Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction

Article Article scientifique Article Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction eng 2015-12 author Pascoli Vincent Jean 703155 author Terrier Jean 121602 author Hiver Agnès 798350 author Luescher Christian 132337 1054-1066 10.1016/j.neuron.2015.10.017 26586182 0896-6273 https://www.sciencedirect.com/science/article/pii/S0896627315008831 The factors causing the transition from recreational drug consumption to addiction remain largely unknown. It has not been tested whether dopamine (DA) is sufficient to trigger this process. Here we use optogenetic self-stimulation of DA neurons of the ventral tegmental area (VTA) to selectively mimic the defining commonality of addictive drugs. All mice readily acquired self-stimulation. After weeks of abstinence, cue-induced relapse was observed in parallel with a potentiation of excitatory afferents onto D1 receptor-expressing neurons of the nucleus accumbens (NAc). When the mice had to endure a mild electric foot shock to obtain a stimulation, some stopped while others persevered. The resistance to punishment was associated with enhanced neural activity in the orbitofrontal cortex (OFC) while chemogenetic inhibition of the OFC reduced compulsivity. Together, these results show that stimulating VTA DA neurons induces behavioral and cellular hallmarks of addiction, indicating sufficiency for the induction and progression of the disease. Animals Channelrhodopsins Clozapine / analogs & derivatives Clozapine / pharmacology Cocaine / administration & dosage Cocaine / pharmacology Cocaine-Related Disorders / pathology Conditioning, Operant / drug effects Conditioning, Operant / physiology Disease Models, Animal Dopamine Plasma Membrane Transport Proteins / genetics Dopamine Plasma Membrane Transport Proteins / metabolism Dopamine Uptake Inhibitors / administration & dosage Dopaminergic Neurons / drug effects Dopaminergic Neurons / physiology Food Deprivation GABA Antagonists / pharmacology Glutamate Decarboxylase / genetics Glutamate Decarboxylase / metabolism Limbic System / drug effects Limbic System / pathology Mice Mice, Inbred C57BL Mice, Transgenic Receptors, Dopamine D1 / genetics Receptors, Dopamine D1 / metabolism Self Administration Sucrose / administration & dosage Synaptic Transmission / drug effects Synaptic Transmission / physiology Time Factors Dewey 616.8 53 Département de neurosciences fondamentales 21A 61 Département des neurosciences cliniques 226 false 271 Mécanismes cellulaires de la dépendance et de l'addiction 520 https://ars.els-cdn.com/content/image/1-s2.0-S0896627315008831-mmc4.mp4 Neuron 88 d581a7e6-b526-4ecf-be78-7e35b7eee247 Article (Published version) Restricted 1-s2.0-S0896627315008831-main.pdf 2885261 application/pdf 27a07df7-b093-40a3-a27f-8a490bf773ea Article (Accepted version) Public Pascoli_Neuron_2015.pdf 3060301 application/pdf 7d6d021e6e414a518f25611adce6c0a5acc6d04f4257f284005199d684cbc882 fe3831bd-53ca-456f-b988-d68d9a2ba9f0 Appendix Public 1-s2.0-S0896627315008831-mmc1.pdf 928499 application/pdf Supplemental Experimental Procedures and Figures S1–S6. f9467540f9d3037b8ad461e24aa7d17635bafb378a5cdf8bc2593edf53c5c0fa 2bc80f05-9af0-4401-ae05-14f92173b93e Supplemental data Public 1-s2.0-S0896627315008831-mmc2.xlsx 55126 application/vnd.openxmlformats-officedocument.spreadsheetml.sheet Table S1. Statistical Analyses. de123a4a859fe3a0e31a63ad04ea872ec9ddbb9593f075bc7517d065f12b88ff openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques

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Sufficiency of Mesolimbic Dopamine Neuron Stimulation for the Progression to Addiction	Neuron	2015	734	264
Globalisation économique et systèmes de formation en Suisse : actes du Colloque du 8 décembre 1998		1999	416	169

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Terrier, Jean