Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling
Open accessAbstract
Endocannabinoids are crucial for the extinction of aversive memories, a process that considerably involves the amygdala. Here, we show that low-frequency stimulation of afferents in the lateral amygdala with 100 pulses at 1 Hz releases endocannabinoids postsynaptically from neurons of the basolateral amygdala of mice in vitro and thereby induces a long-term depression of inhibitory GABAergic synaptic transmission (LTDi) via a presynaptic mechanism. Lowering inhibitory synaptic transmission significantly increases the amplitude of excitatory synaptic currents in principal neurons of the central nucleus, which is the main output site of the amygdala. LTDi involves a selective mGluR1 (metabotropic glutamate receptor 1)-mediated calcium-independent mechanism and the activation of the adenylyl cyclase-protein kinase A pathway. LTDi is abolished by the cannabinoid type 1 (CB1) receptor antagonist SR141716A and cannot be evoked in CB1 receptor-deficient animals. LTDi is significantly enhanced in mice lacking the anandamide-degrading enzyme fatty acid amide hydrolase. The present findings show for the first time that mGluR activation induces a retrograde endocannabinoid signaling via activation of the adenylyl cyclase-protein kinase A pathway and the release of anandamide. Furthermore, the results indicate that anandamide decreases the activity of inhibitory interneurons in the amygdala. This disinhibition increases the activity of common output neurons and could provide a prerequisite for extinction by formation of new memory.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA-CB1 receptor signaling and synaptic plasticity in the BLA.
“Additionally, inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA–CB1 (cannabinoid type 1) receptor signaling and synaptic plasticity in the BLA.”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [51]
CB1R signaling generated by increased AEA can produce long-term depression of inhibitory transmission in the BLA, a change in synaptic plasticity which can serve to promote excitability.
“By contrast, CB1R signaling generated by increased AEA can also produce long-term depression of inhibitory transmission in the BLA, a change in synaptic plasticity which can serve to promote excitability [50,51].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [51]
A CB1R-dependent form of synaptic plasticity in the BLA, long-term depression of inhibitory GABAergic transmission (LTDi), is enhanced by FAAH knockout and by the FAAH inhibitor AM3506 at doses that promote extinction.
“One notable finding is that a CB1R-dependent form of synaptic plasticity in BLA [51,86], long-term depression of inhibitory GABAergic transmission (LTDi), is enhanced by FAAH KO [51] and by the FAAH inhibitor AM3506 at doses that promote extinction [50].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [51]
AEA released during extinction relieves a tonic inhibitory brake on BLA output neurons necessary for the encoding of extinction memories.
“This suggests a scheme in which AEA released during extinction relieves a tonic inhibitory brake on BLA output neurons [50,51,86] necessary for the encoding of extinction memories [102] (Figure 2).”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [51]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
LeDoux, J. E. (2000) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.23.1.155 · Cited by 8,444 · see citing works
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957 · see citing works
Neurons in medial prefrontal cortex signal memory for fear extinction
Milad, M. R., & Quirk, G. J. (2002) · Nature · doi:10.1038/nature01138 · Cited by 1,836 · see citing works
The endogenous cannabinoid system controls extinction of aversive memories
Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., Hermann, H., Tang, J., Hofmann, C., Zieglgänsberger, W., et al. (2002) · Nature · doi:10.1038/nature00839 · Cited by 1,728 · see citing works
Self-citationEndogenous cannabinoids mediate retrograde signalling at hippocampal synapses
Wilson, R. I., & Nicoll, R. A. (2001) · Nature · doi:10.1038/35069076 · Cited by 1,607 · see citing works
Formation and inactivation of endogenous cannabinoid anandamide in central neurons
Marzo, V. D., Fontana, A., Cadas, H., Schinelli, S., Cimino, G., Schwartz, J.-C., & Piomelli, D. (1994) · Nature · doi:10.1038/372686a0 · Cited by 1,585 · see citing works
Role of Endogenous Cannabinoids in Synaptic Signaling
Freund, T. F., Katona, I., & Piomelli, D. (2003) · Physiological Reviews · doi:10.1152/physrev.00004.2003 · Cited by 1,567 · see citing works
A second endogenous cannabinoid that modulates long-term potentiation
Stella, N., Schweitzer, P., & Piomelli, D. (1997) · Nature · doi:10.1038/42015 · Cited by 1,496 · see citing works
Cravatt, B. F., Demarest, K., Patricelli, M. P., Bracey, M. H., Giang, D. K., Martin, B. R., & Lichtman, A. H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.161191698 · Cited by 1,310 · see citing works
Endocannabinoid Signaling in the Brain
Wilson, R. I., & Nicoll, R. A. (2002) · Science · doi:10.1126/science.1063545 · Cited by 1,260 · see citing works
Memory Reconsolidation and Extinction Have Distinct Temporal and Biochemical Signatures
Suzuki, A., Josselyn, S. A., Frankland, P. W., Masushige, S., Silva, A. J., & Kida, S. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5491-03.2004 · Cited by 1,127 · see citing works
Bisogno, T., Howell, F., Williams, G., Minassi, A., Cascio, M. G., Ligresti, A., Matias, I., Schiano-Moriello, A., Paul, P., Williams, E.-J., et al. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200305129 · Cited by 1,039 · see citing works
The role of ventromedial prefrontal cortex in the recovery of extinguished fear
Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-16-06225.2000 · Cited by 957 · see citing works
Marsicano, G., & Lutz, B. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00847.x · Cited by 937 · see citing works
Behavioral and Neural Analysis of Extinction
Myers, K. M., & Davis, M. (2002) · Neuron · doi:10.1016/s0896-6273(02)01064-4 · Cited by 918 · see citing works
Kreitzer, A. C., & Regehr, W. G. (2001) · Neuron · doi:10.1016/s0896-6273(01)00246-x · Cited by 873 · see citing works
Ohno‐Shosaku, T., Maejima, T., & Kano, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00247-1 · Cited by 846 · see citing works
Abe, T., Sugihara, H., Nawa, H., Shigemoto, R., Mizuno, N., & Nakanishi, S. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42219-3 · Cited by 811 · see citing works
Fear conditioning induces a lasting potentiation of synaptic currents in vitro
McKernan, M. G., & Shinnick-Gallagher, P. (1997) · Nature · doi:10.1038/37605 · Cited by 771 · see citing works
Postsynaptic endocannabinoid release is critical to long-term depression in the striatum
Gerdeman, G. L., Ronesi, J. A., & Lovinger, D. M. (2002) · Nature Neuroscience · doi:10.1038/nn832 · Cited by 767 · see citing works
Cannabinoid receptors and pain
Pertwee, R. G. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00031-9 · Cited by 741 · see citing works
Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action
Marzo, V. D., Melck, D. J., Bisogno, T., & PETROCELLIS, L. D. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(98)01283-1 · Cited by 704 · see citing works
Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala
Falls, W., Miserendino, M., & Davis, M. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-03-00854.1992 · Cited by 673 · see citing works
Katona, I., Rancz, E. A., Acsády, L., Ledent, C., Mackie, K., Hájos, N., & Freund, T. F. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-23-09506.2001 · Cited by 668 · see citing works
Manabe, T., Wyllie, D. J., Perkel, D. J., & Nicoll, R. A. (1993) · Journal of Neurophysiology · doi:10.1152/jn.1993.70.4.1451 · Cited by 666 · see citing works
Heterosynaptic LTD of Hippocampal GABAergic Synapses
Chevaleyre, V., & Castillo, P. E. (2003) · Neuron · doi:10.1016/s0896-6273(03)00235-6 · Cited by 647 · see citing works
Endogenous cannabinoids mediate long-term synaptic depression in the nucleus accumbens
Robbe, D., Köpf, M., Rémaury, A., Bockaert, J., & Manzoni, O. J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122149199 · Cited by 631 · see citing works
Chemical characterization of a family of brain lipids that induce sleep
Cravatt, B. F., Prospero-Garcia, O., Siuzdak, G., Gilula, N. B., Henriksen, S. J., Boger, D. L., & Lerner, R. A. (1995) · Science · doi:10.1126/science.7770779 · Cited by 620 · see citing works
Neocortical LTD via Coincident Activation of Presynaptic NMDA and Cannabinoid Receptors
Sjöström, P. J., Turrigiano, G. G., & Nelson, S. B. (2003) · Neuron · doi:10.1016/s0896-6273(03)00476-8 · Cited by 610 · see citing works
Retrograde signaling in the regulation of synaptic transmission: focus on endocannabinoids
Alger, B. E. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00080-1 · Cited by 599 · see citing works
Maejima, T., Hashimoto, K., Yoshida, T., Aiba, A., & Kano, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00375-0 · Cited by 556 · see citing works
Melis, M., Pistis, M., Perra, S., Muntoni, A. L., Pillolla, G., & Gessa, G. L. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4503-03.2004 · Cited by 478 · see citing works
Metabotropic Glutamate Receptors 1 and 5 Differentially Regulate CA1 Pyramidal Cell Function
Mannaioni, G., Marino, M. J., Valenti, O., Traynelis, S. F., & Conn, P. J. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-16-05925.2001 · Cited by 441 · see citing works
Mechoulam, R., Fride, E., & Marzo, V. D. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00649-9 · Cited by 431 · see citing works
Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells
Pitler, T. A., & Alger, B. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-10-04122.1992 · Cited by 414 · see citing works
Metabotropic Glutamate Receptors Drive the Endocannabinoid System in Hippocampus
Varma, N., Carlson, G. C., Ledent, C. A., & Alger, B. E. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-24-j0003.2001 · Cited by 407 · see citing works
Mechanisms of Cannabinoid Inhibition of GABAASynaptic Transmission in the Hippocampus
Hoffman, A. F., & Lupica, C. R. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-07-02470.2000 · Cited by 401 · see citing works
The role of amygdala glutamate receptors in fear learning, fear-potentiated startle, and extinction
Walker, D. L., & Davis, M. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00698-0 · Cited by 356 · see citing works
Sugiura, T., Kobayashi, Y., Oka, S., & Waku, K. (2002) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1054/plef.2001.0356 · Cited by 346 · see citing works
Endocannabinoids facilitate the induction of LTP in the hippocampus
Carlson, G. C., Wang, Y., & Alger, B. E. (2002) · Nature Neuroscience · doi:10.1038/nn879 · Cited by 336 · see citing works
Postsynaptic Induction and PKA-Dependent Expression of LTP in the Lateral Amygdala
Huang, Y.-Y., & Kandel, E. R. (1998) · Neuron · doi:10.1016/s0896-6273(00)80524-3 · Cited by 333 · see citing works
Biosynthesis of an Endogenous Cannabinoid Precursor in Neurons and its Control by Calcium and cAMP
Cadas, H., Gaillet, S., Beltramo, M., Venance, L., & Piomelli, D. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-12-03934.1996 · Cited by 318 · see citing works
Group I metabotropic glutamate receptors: implications for brain diseases
Bordi, F., & Ugolini, A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00095-1 · Cited by 294 · see citing works
Electrophysiological and morphological properties of rat basolateral amygdaloid neurons in vitro
Washburn, M., & Moises, H. C. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-10-04066.1992 · Cited by 270 · see citing works
Lichtman, A. H., Hawkins, E. G., Griffin, G., & Cravatt, B. F. (2002) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.302.1.73 · Cited by 224 · see citing works
Azad, S. C., Eder, M., Marsicano, G., Lutz, B., Zieglgänsberger, W., & Rammes, G. (2003) · Learning & Memory · doi:10.1101/lm.53303 · Cited by 220 · see citing works
Self-citationRodrigues, S. M., Bauer, E. P., Farb, C. R., Schafe, G. E., & LeDoux, J. E. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-12-05219.2002 · Cited by 215 · see citing works
Hoffman, A. F., & Lupica, C. R. (2001) · Journal of Neurophysiology · doi:10.1152/jn.2001.85.1.72 · Cited by 194 · see citing works
Ohno‐Shosaku, T., Shosaku, J., Tsubokawa, H., & Kano, M. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.01929.x · Cited by 179 · see citing works
Inhibition of Interneuron Firing Extends the Spread of Endocannabinoid Signaling in the Cerebellum
Kreitzer, A. C., Carter, A. G., & Regehr, W. G. (2002) · Neuron · doi:10.1016/s0896-6273(02)00695-5 · Cited by 168 · see citing works
Martin, W. J., Coffin, P. O., Attias, E., Balinsky, M., Tsou, K., & Walker, J. M. (1999) · Brain Research · doi:10.1016/s0006-8993(98)01368-7 · Cited by 164 · see citing works
Evidence that GABA transmission mediates context-specific extinction of learned fear
Harris, J. A., & Westbrook, R. F. (1998) · Psychopharmacology · doi:10.1007/s002130050745 · Cited by 164 · see citing works
McDonald, A. J., & Mascagni, F. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00380-3 · Cited by 157 · see citing works
Emerging roles for endocannabinoids in long‐term synaptic plasticity
Gerdeman, G. L., & Lovinger, D. M. (2003) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705466 · Cited by 142 · see citing works
Valenti, O., Conn, P. J., & Marino, M. J. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10081 · Cited by 125 · see citing works
Lavreysen, H., Janssen, C. G. M., Bischoff, F., Langlois, X., Leysen, J. E., & Lesage, A. S. J. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.5.1082 · Cited by 115 · see citing works
Galante, M., & Diana, M. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.0403-04.2004 · Cited by 110 · see citing works
Li, W., & Neugebauer, V. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00485.2003 · Cited by 106 · see citing works
Cannabinoids inhibit GABAergic synaptic transmission in mice nucleus accumbens
Manzoni, O. J., & Bockaert, J. (2001) · European Journal of Pharmacology · doi:10.1016/s0014-2999(01)00723-3 · Cited by 103 · see citing works
Rammes, G., Steckler, T., Kresse, A. E., Schütz, G., Zieglgänsberger, W., & Lutz, B. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00108.x · Cited by 100 · see citing works
Battaglia, G., Bruno, V., Pisani, A., Centonze, D., Catania, M. V., Calabresi, P., & Nicoletti, F. (2001) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2001.0992 · Cited by 97 · see citing works
Watanabe, Y., Ikegaya, Y., Saito, H., & Abe, K. (1995) · Neuroscience Research · doi:10.1016/0168-0102(94)00867-f · Cited by 93 · see citing works
Manning, B. H., Merin, N. M., Meng, I. D., & Amaral, D. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-20-08238.2001 · Cited by 88 · see citing works
Lavreysen, H., Pereira, S. N., Leysen, J. E., Langlois, X., & Lesage, A. S. J. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.11.014 · Cited by 80 · see citing works
The endocannabinoid system: a physiological perspective on its role in psychomotor control
Giuffrida, A., & Piomelli, D. (2000) · Chemistry and Physics of Lipids · doi:10.1016/s0009-3084(00)00193-6 · Cited by 63 · see citing works
Picrotoxin enhances latent extinction of conditioned fear.
McGaugh, J. L., Castellano, C., & Brioni, J. D. (1990) · Behavioral Neuroscience · doi:10.1037//0735-7044.104.2.264 · Cited by 62 · see citing works
Lenz, R. A., & Alger, B. E. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00147.x · Cited by 58 · see citing works
Lee, K., & Boden, P. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.649bd.x · Cited by 48 · see citing works
Masgrau, R., Servitja, J., Young, K. W., Pardo, R., Sarri, E., Nahorski, S. R., & Picatoste, F. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2000.01384.x · Cited by 29 · see citing works
Balázs, R., Miller, S., Chun, Y. S., O'Toole, J., & Cotman, C. W. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70062446.x · Cited by 27 · see citing works
Thomsen, C. (1996) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(96)00042-5 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Endocannabinoid-Mediated Control of Synaptic Transmission
Kano, M., Ohno‐Shosaku, T., Hashimotodani, Y., Uchigashima, M., & Watanabe, M. (2009) · Physiological Reviews · doi:10.1152/physrev.00019.2008 · Cited by 1,529 · see citing works
Myers, K. M., & Davis, M. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001939 · Cited by 1,277 · see citing works
Metaplasticity: tuning synapses and networks for plasticity
Abraham, W. C. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2356 · Cited by 1,119 · see citing works
“Similarly, priming-stimulation-induced iLTD facilitates LTP that is induced at least 60–90 minutes late”
BackgroundPape, H.-C., & Pare, D. (2010) · Physiological Reviews · doi:10.1152/physrev.00037.2009 · Cited by 994 · see citing works
“Moreover, pharmacological blockade of CB1 receptors led to a similar deficit in wild-type mice (16), which was ameliorated with administration of a CCK2 receptor antagonist (72).”
Amygdala inhibitory circuits and the control of fear memory
Ehrlich, I., Humeau, Y., Grenier, F., Ciocchi, S., Herry, C., & Lüthi, A. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.026 · Cited by 878 · see citing works
“A candidate mechanism for the acute changes could be a form of inhibitory long-term depression (LTDi) observed in BLA slices, which is CB1 receptor-dependent and mediated by a decrease in presynaptic GABA release (Azad et al., 2004; Marsicano et al., 2002).”
BackgroundThe Emerging Role of the Endocannabinoid System in Endocrine Regulation and Energy Balance
Pagotto, U., Marsicano, G., Cota, D., Lutz, B., & Pasquali, R. (2005) · Endocrine Reviews · doi:10.1210/er.2005-0009 · Cited by 856 · see citing works
“For instance, electrophysiological and biochemical evidence shows that 2-AG is mostly involved in retrograde control of synaptic activity in the VTA (109), or the hippocampus (112), whereas AEA appears to play an important role in other regions, such as the basal ganglia (113) and the amygdala (114).”
BackgroundENDOCANNABINOID-MEDIATED SYNAPTIC PLASTICITY IN THE CNS
Chevaleyre, V., Takahashi, K. A., & Castillo, P. E. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.29.051605.112834 · Cited by 779 · see citing works
Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors
Agarwal, N., Pacher, P., Tegeder, I., Amaya, F., Constantin, C. E., Brenner, G. J., Rubino, T., Michalski, C. W., Marsicano, G., Monory, K., et al. (2007) · Nature Neuroscience · doi:10.1038/nn1916 · Cited by 571 · see citing works
Endocannabinoid signaling as a synaptic circuit breaker in neurological disease
Katona, I., & Freund, T. F. (2008) · Nature Medicine · doi:10.1038/nm.f.1869 · Cited by 579 · see citing works
“, but, occasionally, mGluR 1 activates the signalin”
BackgroundRegional Brain Abnormalities Associated With Long-term Heavy Cannabis Use
Yücel, M., Solowij, N., Respondek, C., Whittle, S., Fornito, A., Pantelis, C., & Lubman, D. I. (2008) · Archives of General Psychiatry · doi:10.1001/archpsyc.65.6.694 · Cited by 495 · see citing works
Endocannabinoid Signaling and Long-Term Synaptic Plasticity
Heifets, B. D., & Castillo, P. E. (2009) · Annual Review of Physiology · doi:10.1146/annurev.physiol.010908.163149 · Cited by 488 · see citing works
Singewald, N., Schmuckermair, C., Whittle, N., Holmes, A., & Ressler, K. J. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.12.004 · Cited by 390 · see citing works
“The release of anandamide and concomitant CB1-receptor activation induce long-term depression of inhibitory transmission (LTDi) in the BLA (Azad et al., 2004; Gunduz-Cinar et al., 2013b).”
BackgroundKreitzer, A. C., & Malenka, R. C. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2959-05.2005 · Cited by 358 · see citing works
“The postsynaptic mechanisms responsible for triggering eCB-LTD are not well understood, although activation of metabotropic glutamate receptors (mGluRs) is required in the hippocampus, striatum, and amygdala (Sung et al., 2001; Robbe et al., 2002b; Chevaleyre and Castillo, 2003; Azad et al., 2004).”
BackgroundThe Endocannabinoid System: Drug Targets, Lead Compounds, and Potential Therapeutic Applications
Lambert, D. M., & Fowler, C. J. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm058183t · Cited by 350 · see citing works
Gunduz-Cinar, O., MacPherson, K. P., Cinar, R., Gamble-George, J., Sugden, K., Williams, B., Godlewski, G., Ramikie, T. S., Gorka, A. X., Alapafuja, S. O., et al. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.72 · Cited by 307 · see citing works
Hill, M. N., McLaughlin, R. J., Morrish, A. C., Viau, V., Floresco, S. B., Hillard, C. J., & Gorzalka, B. B. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.114 · Cited by 304 · see citing works
“Specifically, AEA signaling within the amygdala mediates forms of synaptic plasticity, such as inhibitory long-term depression, which are conducive to fear extinction and emotional flexibility (Azad et al., 2004).”
BackgroundAkirav, I., & Maroun, M. (2007) · Neural Plasticity · doi:10.1155/2007/30873 · Cited by 277 · see citing works
“[99] have shown that CB1 receptors reduce GABA-ergic synaptic transmission in the amygdale, and consequently facilitate extinction of aversive memories.”
BackgroundSeeking a Spotless Mind: Extinction, Deconsolidation, and Erasure of Fear Memory
Maren, S. (2011) · Neuron · doi:10.1016/j.neuron.2011.04.023 · Cited by 259 · see citing works
“CB1 receptors are localized on inhibitory interneurons in the amygdala (Azad et al., 2004) and may regulate the activity of these neurons during extinction learning (Chhatwal et al., 2005a; Chhatwal et al., 2009).”
BackgroundSupply and demand for endocannabinoids
Alger, B. E., & Kim, J. (2011) · Trends in Neurosciences · doi:10.1016/j.tins.2011.03.003 · Cited by 268 · see citing works
Kullmann, D. M., Moreau, A. W., Bakiri, Y., & Nicholson, E. (2012) · Neuron · doi:10.1016/j.neuron.2012.07.030 · Cited by 234 · see citing works
“The effect was potentiated by blocking anandamide degradation, implying that this eCB, rather than 2-AG, is involved (Azad et al., 2004).”
Gilman, J. M., Kuster, J. K., Lee, S., Lee, M. J., Kim, B. W., Makris, N., van der Kouwe, A., Blood, A. J., & Breiter, H. C. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.4745-13.2014 · Cited by 250 · see citing works
“Second, animal studies have demonstrated that exogenous and endogenous cannabinoids can significantly alter synaptic transmission in the nucleus accumbens (Lupica et al., 2004) and in the amygdala (Azad et al., 2004).”
BackgroundEndocannabinoid-mediated long-term plasticity requires cAMP/PKA signaling and RIM1α
Chevaleyre, V., Heifets, B. D., Kaeser, P. S., Südhof, T. C., & Castillo, P. E. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.020 · Cited by 261 · see citing works
“Furthermore, we tested the generality of these mechanisms in the basolateral amygdala (BLA) where eCBs mediate I-LTD (Azad et al., 2004;Marsicano et al., 2002).”
InfluentialPresynaptic Modulation by Endocannabinoids
Lovinger, D. M. (2007) · Handbook of experimental pharmacology · doi:10.1007/978-3-540-74805-2_14 · Cited by 245 · see citing works
“for EC-LTD in amygdala (Azad et al. 2004), or if these signaling mechanisms are involved in presynaptic EC-LTD maintenance.”
BackgroundAnxiolytic-Like Properties of the Anandamide Transport Inhibitor AM404
Bortolato, M., Campolongo, P., Mangieri, R. A., Scattoni, M. L., Frau, R., Trezza, V., Rana, G. L., Russo, R., Calignano, A., Gessa, G. L., et al. (2006) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301061 · Cited by 233 · see citing works
“…of dopamine signaling and long-term synaptic plasticity in the striatum (Giuffrida et al, 1999; Beltramo et al, 2000; Gerdeman et al, 2002; Azad et al, 2004) as well as acetylcholine signaling in the neocortex and hippocampus (Gifford et al, 1999; Tzavara et al, 2003; Steffens et al,…”
BackgroundAmygdala FAAH and anandamide: mediating protection and recovery from stress
Gunduz-Cinar, O., Hill, M. N., McEwen, B. S., & Holmes, A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.08.008 · Cited by 229 · see citing works
“One notable finding is that a CB1R-dependent form of synaptic plasticity in BLA [51,86], long-term depression of inhibitory GABAergic transmission (LTDi), is enhanced by FAAH KO [51] and by the FAAH inhibitor AM3506 at doses that promote extinction [50].”
BackgroundHill, M. N., Kumar, S. A., Filipski, S. B., Iverson, M., Stuhr, K. L., Keith, J. M., Cravatt, B. F., Hillard, C. J., Chattarji, S., & McEwen, B. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.90 · Cited by 222 · see citing works
The endocannabinoid system: emotion, learning and addiction
Moreira, F. A., & Lutz, B. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00104.x · Cited by 222 · see citing works
“The same may be true in the lateral amygdala, where CB1 receptor-activation may inhibit both GABA and glutamate release (Azad et al. 2003; 2004).”
BackgroundCannabinoid CB1 receptors control conditioned drug seeking
Vries, T. J. D., & Schoffelmeer, A. N. M. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.06.002 · Cited by 219 · see citing works
Long-term plasticity at inhibitory synapses
Castillo, P. E., Chiu, C. Q., & Carroll, R. C. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.01.006 · Cited by 222 · see citing works
“eCB-mediated I-LTD has been identified in the hippocampus [9], amygdala [10,11], dorsal striatum [12], brainstem [13] and visual cortex [14 ].”
Endocannabinoids and Synaptic Function in the CNS
Hashimotodani, Y., Ohno‐Shosaku, T., & Kano, M. (2007) · The Neuroscientist · doi:10.1177/1073858406296716 · Cited by 207 · see citing works
Jung, K., Mangieri, R. A., Stapleton, C. J., Kim, J., Fegley, D., Wallace, M., Mackie, K., & Piomelli, D. (2005) · Molecular Pharmacology · doi:10.1124/mol.105.013961 · Cited by 197 · see citing works
“There are, however, several forms of endocannabinoid-mediated plasticity that do not require Ca(2) for their expression, such as those triggered by muscarinic acetylcholine receptors in the hippocampus (Maejima et al., 2001; Kim et al., 2002; Chevaleyre and Castillo, 2003; Azad et al., 2004; Galante and Diana, 2004).”
InfluentialMonday, H. R., Younts, T. J., & Castillo, P. E. (2018) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-080317-062155 · Cited by 175 · see citing works
“In contrast, preLTP at thalamic inputs onto local amygdala inhibitory interneurons is linked with fear suppression (Bauer & LeDoux 2004), whereas fear extinction in the amygdala appears to involve eCB-mediated iLTD (Lutz 2007, Azad et al. 2004).”
BackgroundCB1 receptor stimulation in specific brain areas differently modulate anxiety-related behaviour
Rubino, T., Guidali, C., Viganò, D., Realini, N., Valenti, M., Massi, P., & Parolaro, D. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.024 · Cited by 179 · see citing works
Endocannabinoid signalling: has it got rhythm?
Vaughn, L. K., Denning, G., Stuhr, K. L., de Wit, H., Hill, M. N., & Hillard, C. J. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00790.x · Cited by 176 · see citing works
Ganon-Elazar, E., & Akirav, I. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.1223-09.2009 · Cited by 173 · see citing works
“Several studies have reported strong inhibition of BLA interneurons after application of CB1 receptor agonists (Azad et al., 2004; Pistis et al., 2004), which is expected to decrease local inhibitory feedback on pyramidal amygdalar outputs neurons.”
BackgroundPresynaptic LTP and LTD of Excitatory and Inhibitory SynapsesPreprint
Castillo, P. E. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005728 · Cited by 169 · see citing works
Laviolette, S. R., & Grace, A. A. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6027-5 · Cited by 170 · see citing works
Patel, S., & Hillard, C. J. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06266.x · Cited by 162 · see citing works
“, 2007), amygdala (Marsicano et al., 2002; Azad et al., 2004), and nucleus accumbens (Robbe et al.”
BackgroundPatel, S., Kingsley, P. J., Mackie, K., Marnett, L. J., & Winder, D. G. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.101 · Cited by 153 · see citing works
“It is also not because of a general impairment in 2-AG signaling because receptor-driven eCB release initiated by 50 mM dihydroxyphenylglycine (B50% eIPSC suppression) is comparable to that observed in BLA and other brain regions (Patel and Winder, unpublished data; (Azad et al, 2004)).”
A role for cannabinoid CB1 receptors in mood and anxiety disorders
Witkin, J. M., Tzavara, E. T., & Nomikos, G. G. (2005) · Behavioural Pharmacology · doi:10.1097/00008877-200509000-00005 · Cited by 156 · see citing works
“the extinction of aversive memories, is enhanced in FAAH KO mice (Azad et al., 2004).”
BackgroundInfluentialMechanisms of synaptic depression triggered by metabotropic glutamate receptors
Bellone, C., Lüscher, C., & Mameli, M. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8263-3 · Cited by 150 · see citing works
Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse
Korpi, E. R., den Hollander, B., Farooq, U., Vashchinkina, E., Rajkumar, R., Nutt, D. J., Hyytiä, P., & Dawe, G. S. (2015) · Pharmacological Reviews · doi:10.1124/pr.115.010967 · Cited by 148 · see citing works
“By using brain slices, HFS of lateral amygdala induces LTD of GABAergic transmission in the BLA, which then increased amplitudes of EPSCs in the neurons of the CeA, the final output nuclei from the amygdala (Azad et al., 2004).”
The Endocannabinoid System of Animals
Silver, R. (2019) · Animals · doi:10.3390/ani9090686 · Cited by 148 · see citing works
“Some of these are: Neuronal plasticity [6], pain [7], anxiety [8], inflammation [9], neuro-inflammation [10], immune function [11], metabolic regulation [12], and bone growth [13].”
BackgroundEndocannabinoid system dysfunction in mood and related disorders
Ashton, C. H., & Moore, P. B. (2011) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2011.01687.x · Cited by 145 · see citing works
“Endocannabinoids also exert an amnesic effect and are crucial for the extinction (forgetting) of aversive memories (91, 92), while blockade of the CB1 receptor induces deficits on the extinction of aversive memories and supersensitivity to stress (74).”
BackgroundChiu, C. Q., Puente, N., Grandes, P., & Castillo, P. E. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0736-10.2010 · Cited by 143 · see citing works
“Thus, similar to the hippocampus (Chevaleyre and Castillo, 2003) and amygdala (Azad et al., 2004), I-LTD in the PFC does not require postsynaptic calcium increases, further bolstering the idea that postsynaptic D2Rs are not involved.”
BackgroundEndocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses
Viveros, M., Marco, E. M., Llorente, R., & López‐Gallardo, M. (2007) · Neural Plasticity · doi:10.1155/2007/52908 · Cited by 144 · see citing works
“[19] showed that low-frequency stimulation of afferents in the lateral amygdala released endocannabinoids postsynaptically from neurons of the basolateral amygdala of mice, and thereby induced an LTP of inhibitory GABAergic synaptic transmission (LTDi) via a presynaptic mechanism.”
BackgroundSzabó, B., Urbanski, M. J., Bisogno, T., Marzo, V. D., Mendiguren, A., Baer, W. U., & Freiman, I. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.119362 · Cited by 141 · see citing works
“However, long-term depression in the amygdala was stronger in mice lacking fatty acid amide hydrolase and not changed by U73122 and RHC80267 – findings pointing to a role of anandamide (Azad et al. 2004).”
BackgroundRoles of the Endocannabinoid System in Learning and Memory
Marsicano, G., & Lafenêtre, P. (2009) · Current topics in behavioral neurosciences · doi:10.1007/978-3-540-88955-7_8 · Cited by 140 · see citing works
Presynaptic long-term plasticity
Yang, Y., & Calakos, N. (2013) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2013.00008 · Cited by 135 · see citing works
Endocannabinoids in Synaptic Plasticity and Neuroprotection
Xu, J., & Chen, C. (2014) · The Neuroscientist · doi:10.1177/1073858414524632 · Cited by 138 · see citing works
Lafenêtre, P., Chaouloff, F., & Marsicano, G. (2007) · Pharmacological Research · doi:10.1016/j.phrs.2007.09.006 · Cited by 135 · see citing works
Lee, S.-H., Ledri, M., Toth, B., Marchionni, I., Henstridge, C. M., Dudok, B., Kenesei, K., Barna, L., Szabo, S. I., Renkecz, T., et al. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.4112-14.2015 · Cited by 133 · see citing works
“, 2009a), emerging evidence indicates that specific forms of phasic and tonic endocannabinoid signaling at given brain circuit locations or under specific physiological conditions are mediated by anandamide (Azad et al., 2004; Kim and Alger, 2010; Huang and Woolley, 2012; Lerner and Kreitzer, 2012; Khlaifia et al., 20…”
BackgroundLópez‐Moreno, J. A., González‐Cuevas, G., Moreno, G., & Navarro, M. A. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00105.x · Cited by 131 · see citing works
“More specifically, the endogenous cannabinoid anandamide could decrease the inhibitory activity of interneurons in the amygdala (Azad et al. 2004).”
BackgroundHill, M. N., Titterness, A. K., Morrish, A. C., Carrier, E. J., Lee, T. T. ‐., Gil‐Mohapel, J., Gorzalka, B. B., Hillard, C. J., & Christie, B. R. (2009) · Hippocampus · doi:10.1002/hipo.20647 · Cited by 129 · see citing works
“Alternately, cAMP-protein kinase signaling has been found to promote AEA synthesis in neuronal cultures and slice preparations (Azad et al., 2004; Cadas et al., 1996; Malcher-Lopes et al., 2006; Vellani et al., 2008) and voluntary exercise is known to increase hippocampal cAMP signaling (Shen et…”
BackgroundRole of CB1 cannabinoid receptors on GABAergic neurons in brain aging
Albayram, Ö., Alferink, J., Pitsch, J., Piyanova, A., Neitzert, K., Poppensieker, K., Mauer, D., Michel, K., Legler, A., Becker, A. J., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016442108 · Cited by 129 · see citing works
“Activation of CB1 receptors on theGABAergic neurons leads to a decrease inGABA release (20, 48) and thus to formation of the depolarization-induced suppression of inhibition (DSI) (35) and long-term depression of inhibitory GABAergic synaptic transmission (LTDi) (49, 50).”
BackgroundLuchicchi, A., & Pistis, M. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8299-0 · Cited by 126 · see citing works
Sumislawski, J. J., Ramikie, T. S., & Patel, S. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.166 · Cited by 124 · see citing works
“As LTDi in the BLA has been demonstrated to involve group-1 metabotropic glutamate receptors (mGluR; Azad et al, 2004), we pretreated slices with a combination of mGluR1 and mGluR5 antagonists (LY456236 (10 mM) and MTEP (10 mM), respectively).”
BackgroundMethodResultInfluentialZhu, P., & Lovinger, D. M. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1148-05.2005 · Cited by 125 · see citing works
“This mGluR-dependent component of DSI may be similar to endocannabinoiddependent long-term depression (LTD) (Gerdeman et al., 2002; Robbe et al., 2002; Chevaleyre and Castillo, 2003; Azad et al., 2004), but additional studies examining the duration of this synaptic depression will be needed to determine whether this i…”
InfluentialThe Endocannabinoid System and Extinction Learning
Lutz, B. (2007) · Molecular Neurobiology · doi:10.1007/s12035-007-8004-x · Cited by 121 · see citing works
“, in amygdala [21, 100, 101], hippocampus [101–104], and prefrontal areas [105].”
BackgroundVariations in the human cannabinoid receptor (CNR1) gene modulate striatal responses to happy faces
Chakrabarti, B., Kent, L., John Suckling, A., Bullmore, E. T., & Baron‐Cohen, S. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04697.x · Cited by 122 · see citing works
“Retrograde endocannabinoid signalling mediated through the CNR1 has been suggested as a possible mechanism for extinction of aversive memories (Azad et al., 2004; Cannich et al., 2004).”
BackgroundNiehaus, J. L., Liu, Y., Wallis, K. T., Egertová, M., Bhartur, S. G., Mukhopadhyay, S., Shi, S., He, H., Selley, D. E., Howlett, A. C., et al. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.039263 · Cited by 121 · see citing works
“Endocannabinoids act as retrograde messengers mediating CB1-dependent forms of short-term synaptic plasticity known as depolarization-induced suppression of inhibition or excitation (Diana and Marty, 2004) and longer-lasting forms of synaptic plasticity, such as long-term depression (Gerdeman and Lovinger, 2001; Robbe…”
BackgroundLötsch, J., Weyer-Menkhoff, I., & Tegeder, I. (2017) · European Journal of Pain · doi:10.1002/ejp.1148 · Cited by 118 · see citing works
Passie, T., Emrich, H. M., Karst, M., Brandt, S. D., & Halpern, J. H. (2012) · Drug Testing and Analysis · doi:10.1002/dta.1377 · Cited by 117 · see citing works
“Endocannabinoids exert an amnesic effect and may be crucial for the extinction of aversive memories,([76,77]) while blockage or knockout of the CB1 receptor induce deficits of the extinction processes and supersensitivity to stress([78]) by decreasing GABAergic function.”
BackgroundYoshida, T., Uchigashima, M., Yamasaki, M., Katona, I., Yamazaki, M., Sakimura, K., Kano, M., Yoshioka, M., & Watanabe, M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1012875108 · Cited by 116 · see citing works
Developmental trajectory of the endocannabinoid system in human dorsolateral prefrontal cortex
Long, L. E., Lind, J., Webster, M. J., & Weickert, C. S. (2012) · BMC Neuroscience · doi:10.1186/1471-2202-13-87 · Cited by 115 · see citing works
“Postsynaptic release and retrograde diffusion of endocannabinoids results in presynaptic CB1R activation and suppression of neurotransmitter release from presynaptic [20,26-31] and, indirectly, from postsynaptic terminals [32].”
BackgroundDevelopmental emergence of fear learning corresponds with changes in amygdala synaptic plasticity
Thompson, J. V., Sullivan, R. M., & Wilson, D. A. (2008) · Brain Research · doi:10.1016/j.brainres.2008.01.057 · Cited by 109 · see citing works
“Both amygdala synaptic plasticity and learned fear aremodulatedbyanumberof factors, including neuromodulators (Rosenkranz and Grace, 2002; Azad et al., 2004), steroid hormones (Setlow et al., 2000) and level of GABAergic inhibition (Watanabe et al., 1995; Rammes et al., 2000).”
BackgroundA therapeutic role for cannabinoid CB1 receptor antagonists in major depressive disorders
Witkin, J. M., Tzavara, E. T., Davis, R. J., Li, X., & Nomikos, G. G. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.10.006 · Cited by 110 · see citing works
Qin, Z., Zhou, X. C., Pandey, N. R., Vecchiarelli, H. A., Stewart, C. A., Zhang, X., Lagace, D. C., Brunel, J. M., Béïque, J.-C., Stewart, A. F. R., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.015 · Cited by 105 · see citing works
“Both responses reflect mGluR5-dependent eCB-mediated alteration in synaptic GABA release (Azad et al., 2004; Marsicano et al., 2002) and were blocked by pretreatment with the CB1R antagonist AM251 (Figures 3B and 3C).”
Bimodal Control of Fear-Coping Strategies by CB 1 Cannabinoid Receptors
Metna‐Laurent, M., Gómez, E. S., Verrier, D., Conforzi, M., Jégo, P., Lafenêtre, P., & Marsicano, G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1054-12.2012 · Cited by 104 · see citing works
“…by CB1 receptors signaling on both inhibitory and excitatory amygdalar neurotransmissions has been recently associated with the temporal adaptation of conditioned freezing responses (Kamprath et al., 2011) and in the control of synaptic plasticity (Marsicano et al., 2002; Azad et al., 2004).”
BackgroundAlcohol Use Disorder: Neurobiology and Therapeutics
Yang, W., Singla, R., Maheshwari, O., Fontaine, C. J., & Gil‐Mohapel, J. (2022) · Biomedicines · doi:10.3390/biomedicines10051192 · Cited by 111 · see citing works
Bergado-Acosta, J. R., Sangha, S., Narayanan, R. T., Obata, K., Pape, H., & Stork, O. (2008) · Learning & Memory · doi:10.1101/lm.705408 · Cited by 103 · see citing works
“…et al. 2005; Mascagni and McDonald 2007; Muller et al. 2007) and are thought to mediate specific aspects of fear memoryrelated information processing within the amygdala (e.g., Quirk et al. 2003; Azad et al. 2004; Marowsky et al. 2005) and hippocampus (Crestani et al. 1999; Gafford et al. 2005).”
BackgroundVries, T. J. D., de Vries, W., Janssen, M. C. W., & Schoffelmeer, A. N. M. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2005.02.021 · Cited by 102 · see citing works
Protective activation of the endocannabinoid system during ischemia in dopamine neurons
Melis, M., Pillolla, G., Bisogno, T., Minassi, A., Petrosino, S., Perra, S., Muntoni, A. L., Lutz, B., Gessa, G. L., & Marsicano, G. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.04.010 · Cited by 101 · see citing works
Functional Relevance of Endocannabinoid-Dependent Synaptic Plasticity in the Central Nervous System
Augustin, S. M., & Lovinger, D. M. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.7b00508 · Cited by 97 · see citing works
Bucherelli, C., Baldi, E., Mariottini, C., Passani, M. B., & Blandina, P. (2006) · Learning & Memory · doi:10.1101/lm.326906 · Cited by 97 · see citing works
Lorenzetti, V., Solowij, N., Fornito, A., Lubman, D. I., & Yücel, M. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990435 · Cited by 96 · see citing works
“, hippocampus [120-122], PFC [123] and amygdala [124-127]) and that have been ascribed to an adverse impact of cannabinoids on the cerebellum [128].”
BackgroundWolf, O. T., Atsak, P., de Quervain, D. J. ‐., Roozendaal, B., & Wingenfeld, K. (2015) · Journal of Neuroendocrinology · doi:10.1111/jne.12353 · Cited by 97 · see citing works
Histamine in the brain: Beyond sleep and memory
Passani, M. B., Giannoni, P., Bucherelli, C., Baldi, E., & Blandina, P. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.12.002 · Cited by 95 · see citing works
“[33] Azad SC, Monory K, Marsicano G, Cravatt BF, Lutz B, Zieglgansberger W, et al.”
BackgroundEndocannabinoid signaling and the hypothalamic-Pituitary-Adrenal axis
Hillard, C. J., Beatka, M., & Sarvaideo, J. (2016) · Comprehensive physiology · doi:10.1002/cphy.c160005 · Cited by 93 · see citing works
CB1 receptor signaling regulates social anxiety and memory
Litvin, Y., Phan, A., Hill, M. N., Pfaff, D. W., & McEwen, B. S. (2013) · Genes Brain & Behavior · doi:10.1111/gbb.12045 · Cited by 93 · see citing works
“This process may be related to structural changes within the basolateral nucleus of the amygdala, as eCBs have been shown to regulate synaptic plasticity in this structure, likely affecting emotionality (Azad et al. 2004; Kodirov et al. 2009; Marsicano et al. 2002).”
BackgroundEndocannabinoid-mediated synaptic plasticity and addiction-related behavior
Sidhpura, N., & Parsons, L. H. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.05.034 · Cited by 92 · see citing works
“, 2010) and have determined that this process is reliant on mGluR1 receptor function (Azad et al., 2004).”
BackgroundTan, H., Lauzon, N. M., Bishop, S. F., Chi, N., Bechard, M., & Laviolette, S. R. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.4718-10.2011 · Cited by 92 · see citing works
“…BLA neuronal population would be expected to increase local inhibitory feedback on BLA projection neurons, as suggested by other neuronal recording studies that have observed strong inhibition of BLA interneurons after application of CB1 receptor agonists (Azad et al., 2004; Pistis et al., 2004).”
BackgroundResultInfluentialTambaro, S., & Bortolato, M. (2011) · Recent Patents on CNS Drug Discovery · doi:10.2174/157488912798842269 · Cited by 89 · see citing works
Atsak, P., Hauer, D., Campolongo, P., Schelling, G., Fornari, R. V., & Roozendaal, B. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.334 · Cited by 85 · see citing works
Alger, B. E. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2011.220855 · Cited by 82 · see citing works
“To account for their results, Azad et al. (2004) propose that release of AEA might be a dynamically regulated step.”
BackgroundCannabinoids and emotionality: a neuroanatomical perspective
McLaughlin, R. J., & Gobbi, G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.052 · Cited by 82 · see citing works
“Furthermore, lowfrequency stimulation of afferents in this amygdala subregion induces a release of AEA postsynaptically from BLA neurons, thereby inducing long-term depression of GABAergic synaptic transmission via a CB1 receptor-dependent presynaptic mechanism (Azad et al., 2004).”
BackgroundModulation of Synaptic Plasticity in the Cortex Needs to Understand All the Players
Meunier, C. N. J., Chameau, P. J. P., & Fossier, P. (2017) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2017.00002 · Cited by 82 · see citing works
“…plasticity has been described in several brain regions such as hippocampus (Chevaleyre and Castillo, 2003), amygdala (Marsicano et al., 2002; Azad et al., 2004), striatum (Adermark and Lovinger, 2009), visual cortex (Jiang et al., 2010) and cerebellum (Pitler and Alger, 1992; Llano et al.,…”
BackgroundTan, H., Lauzon, N. M., Bishop, S. F., Bechard, M. A., & Laviolette, S. R. (2010) · Cerebral Cortex · doi:10.1093/cercor/bhp210 · Cited by 81 · see citing works
“demonstrated a role for CB1 receptor transmission during the processing of neuronal plasticity and emotional associative learning behaviors within this neural circuit (Azad et al. 2004; Laviolette and Grace 2006b; Roche et al. 2007).”
BackgroundResultInfluentialThe Cyclic AMP Cascade Is Altered in the Fragile X Nervous System
Kelley, D. J., Davidson, R. J., Elliott, J. L., Lahvis, G. P., Yin, J. C. P., & Bhattacharyya, A. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000931 · Cited by 81 · see citing works
“Several lines of evidence support the view that mGluR and cAMP mediated pathways functionally interact in platelets [26], lymphocytes [27], neurons [28–32] and astrocytes [33].”
ResultChhatwal, J. P., Gutman, A. R., Maguschak, K. A., Bowser, M. E., Yang, Y., Davis, M., & Ressler, K. J. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.97 · Cited by 80 · see citing works
Seillier, A., Martinez, A. A., & Giuffrida, A. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.81 · Cited by 79 · see citing works
“In the amygdala, however, endocannabinoid-mediated plastic changes have been shown to involve AEA release through activation of a cyclic adenosine monophosphate-protein kinase A (cAMP-PKA)-dependent pathway (Azad et al, 2004).”
BackgroundThe Role of Cannabinoid Receptors in the Descending Modulation of Pain
Palazzo, E., Luongo, L., de Novellis, V., Rossi, F., & Maione, S. (2010) · Pharmaceuticals · doi:10.3390/ph3082661 · Cited by 78 · see citing works
“of the brain, including the striatum [62], hippocampus [63-68], midbrain [69], and amygdala [70,71].”
BackgroundBlockade of amygdala metabotropic glutamate receptor subtype 1 impairs fear extinction
Kim, J., Lee, S., Park, H., Song, B., Hong, I., Geum, D., Shin, K., & Choi, S. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.01.125 · Cited by 78 · see citing works
“[14] has provided evidence that mGluR1 activation in inhibitory neurons in the basolateral amygdala induces activation of endocannabinoid signaling which is required for fear extinction.”
BackgroundThe endocannabinoid signaling system: Pharmacological and therapeutic aspects
Fowler, C. J., Holt, S., Nilsson, O. R., Jonsson, K., Tiger, G., & Jacobsson, S. O. P. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.01.023 · Cited by 76 · see citing works
“In contrast, in the amygdala, endocannabinoid-mediated long-term depression of inhibitory GABAergic synaptic transmission is enhanced in FAAH / mice (Azad et al., 2004), whereas in other systems, 2-AG may be more important (Melis et al., 2004; Makara et al., 2004).”
Role of the basolateral nucleus of the amygdala in endocannabinoid-mediated stress-induced analgesia
Connell, K., Bolton, N., Olsen, D., Piomelli, D., & Hohmann, A. G. (2005) · Neuroscience Letters · doi:10.1016/j.neulet.2005.12.008 · Cited by 76 · see citing works
“Endocannabinoid LTDi in the BLA in turn, enhances excitatory synaptic transmission in the CeA [2].”
InfluentialInput-specific plasticity at excitatory synapses mediated by endocannabinoids in the dentate gyrus
Chiu, C. Q., & Castillo, P. E. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.026 · Cited by 73 · see citing works
“Given previous findings that group I mGluR agonists can trigger eCB release and induce LTD in several brain structures (Azad et al., 2004; Neuropharmacology.”
BackgroundTan, H., Ahmad, T., Loureiro, M., Zunder, J. S., & Laviolette, S. R. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00073 · Cited by 72 · see citing works
“High levels of CB1 receptors are localized in the BLA region of the amygdala (2, 6) and CB1 transmission within the BLA is involved in the regulation of associative learning and memory processing (50, 51).”
BackgroundCannabinoid modulation of drug reward and the implications of marijuana legalization
Covey, D. P., Wenzel, J. M., & Cheer, J. F. (2014) · Brain Research · doi:10.1016/j.brainres.2014.11.034 · Cited by 75 · see citing works
Adermark, L., & Lovinger, D. M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3842-08.2009 · Cited by 71 · see citing works
“This finding is in line with data from the hippocampus and basolateral amygdala indicating that glutamatergic synaptic activation of group I mGluRs is critical for afferent stimulus-induced LTD at inhibitory synapses (Azad et al., 2004; Chevaleyre and Castillo, 2003).”
ResultDendritic signalling and homeostatic adaptation
Yu, L. M. Y., & Goda, Y. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.07.002 · Cited by 70 · see citing works
“Interestingly, a form of endocannabinoid-mediated amygdalar heterosynaptic LTD [60] was triggered using a low-frequency stimulation (1 Hz) not too dissimilar to the frequencies (2 Hz) adopted by Branco et al.”
MethodInfluential
- Authors
- Azad, S. C., Monory, K., Marsicano, G., Cravatt, B. F., Lutz, B., Zieglgänsberger, W., & Rammes, G.
- Affiliations
- Max Planck Institute of Psychiatry (DE)
- Scripps Research Institute (US)
- TUM Klinikum (DE)
- Corresponding author
- Azad, Shahnaz C.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-11-03
- Volume
- 24
- Issue
- 44
- Pages
- 9953-9961
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6730232
- OpenAlex
- W2158593571
- Cited by
- 263
- References
- 71
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 5 · 2022: 11 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 15 · 2014: 17 · 2013: 13 · 2012: 15
- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB 391)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- endocannabinoid signaling, amygdala, associative plasticity, fear extinction, anandamide, CB1 receptor, mGluR1, long-term depression, synaptic inhibition, fatty acid amide hydrolase, basolateral amygdala, central amygdala, inhibitory interneurons, disinhibition, aversive memory
- MeSH terms
- Fatty Acid Amide Hydrolases, Adenylyl Cyclases, Amidohydrolases, Amygdala, Animals, Calcium, gamma-Aminobutyric Acid, Lipoprotein Lipase, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Neural Inhibition, Neuronal Plasticity, Type C Phospholipases, Synapses, Cyclic AMP-Dependent Protein Kinases, Receptors, Metabotropic Glutamate, Mice, Knockout, GTP-Binding Proteins, Receptor, Cannabinoid, CB1, Mice, Cannabinoid Receptor Modulators, Endocannabinoids, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
