The DOI matches its Crossref record; 59 of the 59 references it cites were found in a registry or an index.
Distribution of CB1 Cannabinoid Receptors in the Amygdala and their Role in the Control of GABAergic Transmission
Open accessAbstract
Cannabinoids are the most popular illicit drugs used for recreational purposes worldwide. However, the neurobiological substrate of their mood-altering capacity has not been elucidated so far. Here we report that CB1 cannabinoid receptors are expressed at high levels in certain amygdala nuclei, especially in the lateral and basal nuclei, but are absent in other nuclei (e.g., in the central nucleus and in the medial nucleus). Expression of the CB1 protein was restricted to a distinct subpopulation of GABAergic interneurons corresponding to large cholecystokinin-positive cells. Detailed electron microscopic investigation revealed that CB1 receptors are located presynaptically on cholecystokinin-positive axon terminals, which establish symmetrical GABAergic synapses with their postsynaptic targets. The physiological consequence of this particular anatomical localization was investigated by whole-cell patch-clamp recordings in principal cells of the lateral and basal nuclei. CB1 receptor agonists WIN 55,212-2 and CP 55,940 reduced the amplitude of GABA(A) receptor-mediated evoked and spontaneous IPSCs, whereas the action potential-independent miniature IPSCs were not significantly affected. In contrast, CB1 receptor agonists were ineffective in changing the amplitude of IPSCs in the rat central nucleus and in the basal nucleus of CB1 knock-out mice. These results suggest that cannabinoids target specific elements in neuronal networks of given amygdala nuclei, where they presynaptically modulate GABAergic synaptic transmission. We propose that these anatomical and physiological features, characteristic of CB1 receptors in several forebrain regions, represent the neuronal substrate for endocannabinoids involved in retrograde synaptic signaling and may explain some of the emotionally relevant behavioral effects of cannabinoid exposure.
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“Following their synthesis, ECBs are retrogradely transported into the extracellular space to bind ECB receptors present on presynaptic terminals [19–21].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [19]
In the citing paper
“Within amygdala subnuclei, FAAH is highly expressed on pyramidal neurons in the BLA, and to a significantly lesser extent in the central nucleus (CeA) [19,20,46,47].”
From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [19]
In the citing paper
“Yet, CB1 receptors are expressed at high levels in the BLA (Herkenham et al, 1990;Katona et al, 2001;Tsou et al, 1997)”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as Katona et al, 2001
In the citing paper
“but their expression in the central amygdala is less clear (Katona et al, 2001;Tsou et al, 1997;Cota et al, 2007; but see Kamprath et al, 2011).”
From Cannabinoids prevent the development of behavioral and endocrine alterations in a rat model of intense stress (2012) · cites this paper as Katona et al, 2001
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Ledent, C. A., Valverde, O., Cossu, G., Petitet, F., Aubert, J.-F., Beslot, F., Böhme, G. A., Impérato, A., Pedrazzini, T., Roques, B. P., et al. (1999) · Science · doi:10.1126/science.283.5400.401 · Cited by 3,628
Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses
Wilson, R. I., & Nicoll, R. A. (2001) · Nature · doi:10.1038/35069076 · Cited by 1,607
Immunohistochemical distribution of cannabinoid CB1 receptors in the rat central nervous system
Tsou, K., Brown, S., Sañudo-Peña, M. C., Mackie, K., & Walker, J. M. (1998) · Neuroscience · doi:10.1016/s0306-4522(97)00436-3 · Cited by 1,586
Katona, I., Sperlágh, B., Sı́k, A., Käfalvi, A., Vizi, E. S., Mackie, K., & Freund, T. F. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04544.1999 · Cited by 1,218
Tanda, G., Pontieri, F. E., & Chiara, G. D. (1997) · Science · doi:10.1126/science.276.5321.2048 · Cited by 1,085
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Zimmer, A., Zimmer, A. M., Hohmann, A. G., Herkenham, M. A., & Bonner, T. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5780 · Cited by 1,078
Marsicano, G., & Lutz, B. (1999) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1999.00847.x · Cited by 937
Kreitzer, A. C., & Regehr, W. G. (2001) · Neuron · doi:10.1016/s0896-6273(01)00246-x · Cited by 899
Ohno‐Shosaku, T., Maejima, T., & Kano, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00247-1 · Cited by 874
Mailleux, P., & Vanderhaeghen, J. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90409-u · Cited by 660
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International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W. A., Felder, C. C., Herkenham, M., Mackie, K., Martin, B. R., et al. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.161 · Cited by 2,819
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pacher, P., Bátkai, S., & Kunos, G. (2006) · Pharmacological Reviews · doi:10.1124/pr.58.3.2 · Cited by 2,077
“…and anterior cingular cortex, key regions in the regulation of anxiety, may suggest that the endocannabinoid system plays a role in the control of anxiety (Herkenham et al., 1990, 1991a,b; Glass et al., 1997b; Katona et al., 2001; Hájos and Freund, 2002; Tzavara et al., 2003; Pistis et al., 2004).”
BackgroundThe molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957
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
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 1,616
“In support of this idea, correlated light and electron microscopy using high-resolution immunogold technique provide clear-cut evidence that the CB1 immunostaining visualizing cell bodies and proximal dendrites of interneurons at the light microscopical level is always associated with intracellular organelles, but nev…”
BackgroundResultInfluential
Metadata
- Authors
- Katona, I., Rancz, E. A., Acsády, L., Ledent, C., Mackie, K., Hájos, N., & Freund, T. F.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Université Libre de Bruxelles (BE)
- University of Washington (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-12-01
- Volume
- 21
- Issue
- 23
- Pages
- 9506-9518
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763903
- OpenAlex
- W2153392906
- Cited by
- 668
- References
- 59
- Citations by year
- 2026: 10 · 2025: 22 · 2024: 18 · 2023: 20 · 2022: 31 · 2021: 29 · 2020: 33 · 2019: 18 · 2018: 20 · 2017: 36 · 2016: 37 · 2015: 34 · 2014: 27 · 2013: 29 · 2012: 26
- FWCI
- 13.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Hungarian Scientific Research Fund (T032251)
- National Institutes of Health (5k01da000285-04)
- National Institute on Drug Abuse (DA 00285, DA11322, R01DA011322)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 41301, P30DK041301)
- National Institute of Neurological Disorders and Stroke (NS30549)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- CB1 receptor, amygdala, GABAergic neurotransmission, cholecystokinin interneurons, presynaptic modulation, endocannabinoids, lateral amygdala, basal amygdala, cannabinoid receptor agonists, CB1 knockout mice, emotional behavior
- MeSH terms
- Amygdala, Analgesics, Animals, Cannabinoids, Cholecystokinin, Cyclohexanols, gamma-Aminobutyric Acid, Interneurons, Male, Membrane Potentials, Morpholines, Naphthalenes, Nerve Net, Neural Inhibition, Synaptic Transmission, Organ Specificity, Receptors, Drug, Receptors, GABA-A, Rats, Wistar, Presynaptic Terminals, Mice, Knockout, Patch-Clamp Techniques, Receptors, Cannabinoid, Benzoxazines, Mice, Rats, Cannabinoid Receptor Modulators
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