Drugs of abuse and stress impair LTP at inhibitory synapses in the ventral tegmental area
Open accessAbstract
Synaptic plasticity in the ventral tegmental area (VTA) is modulated by drugs of abuse and stress and is hypothesized to contribute to specific aspects of addiction. Both excitatory and inhibitory synapses on dopamine neurons in the VTA are capable of undergoing long‐term changes in synaptic strength. While the strengthening or weakening of excitatory synapses in the VTA has been widely examined, the role of inhibitory synaptic plasticity in brain reward circuitry is less established. Here, we investigated the effects of drugs of abuse, as well as acute stress, on long‐term potentiation of GABAergic synapses onto VTA dopamine neurons (LTP GABA). Morphine (10 mg/kg i.p.) reduced the ability of inhibitory synapses in midbrain slices to express LTP GABA both at 2 and 24 h after drug exposure but not after 5 days. Cocaine (15 mg/kg i.p.) impaired LTP GABA 24 h after exposure, but not at 2 h. Nicotine (0.5 mg/kg i.p.) impaired LTP GABA 2 h after exposure, but not after 24 h. Furthermore, LTP GABA was completely blocked 24 h following brief exposure to a stressful stimulus, a forced swim task. Our data suggest that drugs of abuse and stress trigger a common modification to inhibitory plasticity, synergizing with their collective effect at excitatory synapses. Together, the net effect of addictive substances or stress is expected to increase excitability of VTA dopamine neurons, potentially contributing to the early stages of addiction.
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Exposure to a single acute stressor can promote long-lasting neuroplastic changes in VTA dopamine neurons in a manner similar to exposure to recreational drugs.
“Exposure to a single acute stressor can also promote long-lasting neuroplastic changes in VTA dopamine neurons in a manner similar to exposure to recreational drugs (Dong et al., 2004; Graziane et al., 2013; Niehaus et al., 2010; Saal et al., 2003).”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Niehaus et al., 2010
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Cites
Molecular basis of long-term plasticity underlying addiction
Nestler, E. J. (2001) · Nature reviews. Neuroscience · doi:10.1038/35053570 · Cited by 1,857 · see citing works
Synaptic plasticity and addiction
Kauer, J. A., & Malenka, R. C. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2234 · Cited by 1,397 · see citing works
Self-citationIs there a common molecular pathway for addiction?
Nestler, E. J. (2005) · Nature Neuroscience · doi:10.1038/nn1578 · Cited by 1,388 · see citing works
Drugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons
Saal, D., Dong, Y., Bonci, A., & Malenka, R. C. (2003) · Neuron · doi:10.1016/s0896-6273(03)00021-7 · Cited by 1,147 · see citing works
Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons
Ungless, M. A., Whistler, J. L., Malenka, R. C., & Bonci, A. (2001) · Nature · doi:10.1038/35079077 · Cited by 1,106 · see citing works
Wise, R. A. (1996) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(96)80079-1 · Cited by 1,072 · see citing works
Koob, G. F., Sanna, P. P., & Bloom, F. E. (1998) · Neuron · doi:10.1016/s0896-6273(00)80557-7 · Cited by 1,026 · see citing works
Nitric oxide as modulator of neuronal function
Prast, H., & Philippu, A. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00044-7 · Cited by 937 · see citing works
Nicotine activates and desensitizes midbrain dopamine neurons
Pidoplichko, V. I., DeBiasi, M., Williams, J. T., & Dani, J. A. (1997) · Nature · doi:10.1038/37120 · Cited by 769 · see citing works
Stress-induced relapse to heroin and cocaine seeking in rats: a review
Shaham, Y., Erb, S. M., & Stewart, J. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00024-2 · Cited by 703 · see citing works
Synaptic mechanisms underlie nicotine-induced excitability of brain reward areas
Mansvelder, H. D., Keath, J. R., & McGehee, D. S. (2002) · Neuron · doi:10.1016/s0896-6273(02)00625-6 · Cited by 701 · see citing works
The role of stress in drug self-administration
Piazza, P. V., & Moal, M. L. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(97)01115-2 · Cited by 674 · see citing works
RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone
Schoch, S., Castillo, P. E., Jo, T., Mukherjee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R. C., & Südhof, T. C. (2002) · Nature · doi:10.1038/415321a · Cited by 579 · see citing works
NO-independent regulatory site on soluble guanylate cyclase
Stasch, J., Becker, E. M., Alonso‐Alija, C., Apeler, H., Dembowsky, K., Feurer, A., Gerzer, R., Minuth, T., Perzborn, E., Pleiß, U., et al. (2001) · Nature · doi:10.1038/35065611 · Cited by 546 · see citing works
Margolis, E. B., Lock, H., Hjelmstad, G. O., & Fields, H. L. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.117069 · Cited by 527 · see citing works
Limbic and Motor Circuitry Underlying Footshock-Induced Reinstatement of Cocaine-Seeking Behavior
McFarland, K., Davidge, S. B., Lapish, C. C., & Kalivas, P. W. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4177-03.2004 · Cited by 524 · see citing works
Behavioural stress facilitates the induction of long-term depression in the hippocampus
Xu, L., Anwyl, R., & Rowan, M. J. (1997) · Nature · doi:10.1038/387497a0 · Cited by 509 · see citing works
Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus
Shors, T. J., Seib, T. B., Levine, S., & Thompson, R. F. (1989) · Science · doi:10.1126/science.2704997 · Cited by 458 · see citing works
Behavioral stress modifies hippocampal plasticity through N-methyl-D-aspartate receptor activation.
Kim, J. J., Foy, M. R., & Thompson, R. F. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4750 · Cited by 435 · see citing works
Bellone, C., & Lüscher, C. (2006) · Nature Neuroscience · doi:10.1038/nn1682 · Cited by 429 · see citing works
RIM1α is required for presynaptic long-term potentiation
Castillo, P. E., Schoch, S., Schmitz, F., Südhof, T. C., & Malenka, R. C. (2002) · Nature · doi:10.1038/415327a · Cited by 389 · see citing works
The Role of Corticotropin-Releasing Factor in Drug Addiction
Sarnyai, Z., Shaham, Y., & Heinrichs, S. C. (2001) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01492-3 · Cited by 381 · see citing works
Wang, B., Shaham, Y., Zitzman, D., Azari, S., Wise, R. A., & You, Z.-B. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0955-05.2005 · Cited by 369 · see citing works
Wooltorton, J. R. A., Pidoplichko, V. I., Broide, R. S., & Dani, J. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-08-03176.2003 · Cited by 363 · see citing works
Chen, B. T., Bowers, M. S., Martín, M., Hopf, F. W., Guillory, A. M., Carelli, R. M., Chou, J., & Bonci, A. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.024 · Cited by 350 · see citing works
Social stress, therapeutics and drug abuse: Preclinical models of escalated and depressed intake
MICZEK, K., YAP, J., & COVINGTONIII, H. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.07.006 · Cited by 338 · see citing works
Cocaine-evoked synaptic plasticity: persistence in the VTA triggers adaptations in the NAc
Mameli, M., Halbout, B., Creton, C., Engblom, D., Parkitna, J. M. R., Spanagel, R., & Lüscher, C. (2009) · Nature Neuroscience · doi:10.1038/nn.2367 · Cited by 335 · see citing works
Dopaminergic Innervation of the Amygdala Is Highly Responsive to Stress
Inglis, F., & Moghaddam, B. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0721088.x · Cited by 310 · see citing works
Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons
Liu, Q.-S., Pu, L., & Poo, M. (2005) · Nature · doi:10.1038/nature04050 · Cited by 305 · see citing works
Opioids block long-term potentiation of inhibitory synapses
Nugent, F. S., Penick, E. C., & Kauer, J. A. (2007) · Nature · doi:10.1038/nature05726 · Cited by 297 · see citing works
Self-citationWhite, F. J., Hu, X. T., Zhang, X., & Wolf, M. E. (1995) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)09601-6 · Cited by 291 · see citing works
Borgland, S. L., Malenka, R. C., & Bonci, A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1312-04.2004 · Cited by 289 · see citing works
Neurotrophic factors and structural plasticity in addiction
Russo, S. J., Mazei‐Robison, M. S., Ables, J. L., & Nestler, E. J. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.059 · Cited by 271 · see citing works
Wanat, M. J., Hopf, F. W., Stuber, G. D., Phillips, P. E. M., & Bonci, A. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.150078 · Cited by 256 · see citing works
Mechanism and Time Course of Cocaine-Induced Long-Term Potentiation in the Ventral Tegmental Area
Argilli, E., Sibley, D. R., Malenka, R. C., England, P. M., & Bonci, A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1001-08.2008 · Cited by 243 · see citing works
Glutamate Receptors on Dopamine Neurons Control the Persistence of Cocaine Seeking
Engblom, D., Bilbao, A., Sanchis‐Segura, C., Dahan, L., Perreau‐Lenz, S., Balland, B., Parkitna, J. M. R., Luján, R., Halbout, B., Mameli, M., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.07.010 · Cited by 238 · see citing works
Zhang, X. F., Hu, X.-T., White, F. J., & Wolf, M. E. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36671-6 · Cited by 210 · see citing works
Laviolette, S. R., Gallegos, R. A., Henriksen, S. J., & van der Kooy, D. (2004) · Nature Neuroscience · doi:10.1038/nn1182 · Cited by 203 · see citing works
Melis, M., Camarini, R., Ungless, M. A., & Bonci, A. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-06-02074.2002 · Cited by 196 · see citing works
Korotkova, T. M., Brown, R. E., Sergeeva, O. A., Ponomarenko, A. A., & Haas, H. L. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04792.x · Cited by 162 · see citing works
cGMP Signalling in the Mammalian Brain: Role in Synaptic Plasticity and Behaviour
Kleppisch, T., & Feil, R. (2009) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-540-68964-5_24 · Cited by 161 · see citing works
Dong, Y., Saal, D., Thomas, M., Faust, R., Bonci, A., Robinson, T., & Malenka, R. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401553101 · Cited by 158 · see citing works
Amphetamine Blocks Long-Term Synaptic Depression in the Ventral Tegmental Area
Jones, S., Gutlerner, J. L., & Kauer, J. A. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-15-05575.2000 · Cited by 151 · see citing works
Self-citationA ventral tegmental CRF–glutamate–dopamine interaction in addiction
Wise, R. A., & Morales, M. (2009) · Brain Research · doi:10.1016/j.brainres.2009.09.101 · Cited by 111 · see citing works
Faleiro, L. J., Jones, S., & Kauer, J. A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300495 · Cited by 76 · see citing works
Self-citationPKG and PKA Signaling in LTP at GABAergic Synapses
Nugent, F. S., Niehaus, J. L., & Kauer, J. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.5 · Cited by 73 · see citing works
Self-citationEnhancement of learning behaviour by a potent nitric oxide‐guanylate cyclase activator YC‐1
Chien, W., Liang, K., Teng, C., Kuo, S., Lee, F., & Fu, W. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03993.x · Cited by 72 · see citing works
Bonci, A., & Borgland, S. (2009) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.024 · Cited by 64 · see citing works
Stress and rodent models of drug addiction: role of VTA–accumbens–PFC–amygdala circuit
Yap, J. J., & Miczek, K. A. (2008) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2009.03.010 · Cited by 57 · see citing works
Florán, B., Barajas, C., Florán, L., et al. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00479-7 · Cited by 55 · see citing works
Lachamp, P. M., Liu, Y., & Liu, S. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2354-08.2009 · Cited by 46 · see citing works
Plasticity of Addiction: A Mesolimbic Dopamine Short‐Circuit?
Niehaus, J. L., Cruz‐Bermúdez, N. D., & Kauer, J. A. (2009) · The American Journal on Addictions · doi:10.1080/10550490902925946 · Cited by 42 · see citing works
Self-citationImpact of basic FGF expression in astrocytes on dopamine neuron synaptic function and development
Forget, C., Stewart, J., & Trudeau, L. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04570.x · Cited by 24 · see citing works
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- Malenka RC Bear MF LTP and LTD: an embarrassment of riches Neuron 2004 44 5 21 15450156
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Drug-evoked synaptic plasticity in addiction: from molecular changes to circuit remodeling
Lüscher, C., & Malenka, R. C. (2011) · Neuron · doi:10.1016/j.neuron.2011.01.017 · Cited by 1,105 · see citing works
One Is Not Enough: Understanding and Modeling Polysubstance Use
Crummy, E. A., O’Neal, T. J., Baskin, B. M., & Ferguson, S. M. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00569 · Cited by 351 · see citing works
Ventral tegmental area dopamine revisited: effects of acute and repeated stress
Holly, E. N., & Miczek, K. A. (2016) · Psychopharmacology · doi:10.1007/s00213-015-4151-3 · Cited by 265 · 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
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Graziane, N. M., Polter, A. M., Briand, L. A., Pierce, R. C., & Kauer, J. A. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.034 · Cited by 121 · see citing works
Self-citationThe effects of psychosocial stress on dopaminergic function and the acute stress response
Bloomfield, M. A., McCutcheon, R. A., Kempton, M., Freeman, T. P., & Howes, O. (2019) · eLife · doi:10.7554/elife.46797 · Cited by 112 · see citing works
“Exposure to a single acute stressor can also promote long-lasting neuroplastic changes in VTA dopamine neurons in a manner similar to exposure to recreational drugs (Dong et al., 2004; Graziane et al., 2013; Niehaus et al., 2010; Saal et al., 2003).”
Simms, J. A., Haass-Koffler, C. L., Bito-Onon, J., Li, R., & Bartlett, S. E. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.268 · Cited by 97 · see citing works
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Brielmaier, J., McDonald, C. G., & Smith, R. F. (2012) · Psychopharmacology · doi:10.1007/s00213-011-2378-1 · Cited by 54 · see citing works
- Authors
- Niehaus, J. L., Murali, M., & Kauer, J. A.
- Affiliations
- Brown University (US)
- Corresponding author
- Kauer, Julie A.
- ORCID
- Kauer, Julie A.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2010-07
- Volume
- 32
- Issue
- 1
- Pages
- 108-117
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC2908505
- OpenAlex
- W2164154357
- Cited by
- 140
- References
- 53
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 6 · 2020: 14 · 2019: 5 · 2018: 8 · 2017: 12 · 2016: 4 · 2015: 14 · 2014: 12 · 2013: 8 · 2012: 8
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Brown University
- National Institutes of Health
- National Institute on Drug Abuse (F32DA024527, DA011289, R01DA011289, DA024527)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- drugs of abuse, acute stress, long-term potentiation, inhibitory synapses, ventral tegmental area, dopaminergic neurons, GABAergic synapses, synaptic plasticity, morphine, cocaine, nicotine, addiction, brain reward system
- MeSH terms
- Analgesics, Opioid, Animals, Cocaine, Dopamine, gamma-Aminobutyric Acid, Morphine, Neurons, Nicotine, Receptors, Glucocorticoid, Illicit Drugs, Stress, Physiological, Synapses, Rats, Sprague-Dawley, Ventral Tegmental Area, Long-Term Potentiation, Patch-Clamp Techniques, Nicotinic Agonists, Dopamine Uptake Inhibitors, Rats
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