Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area

Article Article scientifique Article Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area eng 2013 author Bocklisch Christina 680999 author Pascoli Vincent Jean 703155 author Wong Jovi Chau-Yee 704696 author House David 770289 author Yvon Cédric Marcel 105566 author De Roo Mathias 629721 author Luescher Christian 132337 author Tan Kelly 666575 1521-1525 10.1126/science.1237059 24072923 0036-8075 https://www.science.org/doi/10.1126/science.1237059 Drug-evoked synaptic plasticity in the mesolimbic system reshapes circuit function and drives drug-adaptive behavior. Much research has focused on excitatory transmission in the ventral tegmental area (VTA) and the nucleus accumbens (NAc). How drug-evoked synaptic plasticity of inhibitory transmission affects circuit adaptations remains unknown. We found that medium spiny neurons expressing dopamine (DA) receptor type 1 (D1R-MSNs) of the NAc project to the VTA, strongly preferring the GABA neurons of the VTA. Repeated in vivo exposure to cocaine evoked synaptic potentiation at this synapse, occluding homosynaptic inhibitory long-term potentiation. The activity of the VTA GABA neurons was thus reduced and DA neurons were disinhibited. Cocaine-evoked potentiation of GABA release from D1R-MSNs affected drug-adaptive behavior, which identifies these neurons as a promising target for novel addiction treatments. Animals Cocaine / pharmacology Cocaine-Related Disorders / physiopathology Dopaminergic Neurons / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Neuronal Plasticity / drug effects Synaptic Transmission / drug effects Synaptic Transmission / physiology Ventral Tegmental Area / metabolism Gamma-Aminobutyric Acid / drug effects Gamma-Aminobutyric Acid / metabolism Dewey 616.8 53 Département de neurosciences fondamentales 21A false 271 Mécanismes cellulaires de la dépendance et de l'addiction 520 Science 341 6153 8465a3e9-c330-4c96-b4c9-3a5a1775bca5 Article (Published version) Restricted Bocklisch september 2013.pdf 1998826 application/pdf 32abc1a2-d1f7-4853-8dfc-c1eb20b9101e Article (Accepted version) Public Bocklisch_Science_2013.pdf 1646321 application/pdf 2b8c6727601330ed7be3e459868e06c8f22c7925c42703cfe4f23dd61d2aaa53 0467fce7-ea27-4818-a7ab-c845d5e2de6a Appendix Public bocklisch.sm.pdf 953422 application/pdf Materials and Methods, Figs. S1 to S5 0f77d378f5df7d1bf77cc1d119f08623a895205f2f0435d95f93bf240a3a9813 openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales

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Cocaine disinhibits dopamine neurons by potentiation of GABA transmission in the ventral tegmental area	Science			2013	723	514

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