title: Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats.
abstract: Whereas the majority of cocaine users quit as they experience the negative consequences of drug use, some lose control over their drug taking and compulsively seek drugs. We report that 20% of rats compulsively seek cocaine despite intermittent negative outcomes after escalating their cocaine self-administration. This compulsive subgroup showed marked reductions in forebrain serotonin utilization; increasing serotonin transmission reduced their compulsive cocaine seeking. Depleting forebrain serotonin induced compulsive cocaine seeking in rats with a limited cocaine taking history; this was reversed by systemic treatment with a 5-hydroxytryptamine (5-HT2C) receptor agonist and mimicked by systemic treatment with a 5-HT2C receptor antagonist in intact animals. These results indicate the causal involvement of reduced serotoninergic transmission in the emergence of compulsive drug seeking after a long cocaine-taking history.
authors: Behavioural and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK. yann.pelloux@univ-amu.fr
authors: Yann
authors: Y
authors: Pelloux
authors: Ruth
authors: R
authors: Dilleen
authors: Daina
authors: D
authors: Economidou
authors: David
authors: D
authors: Theobald
authors: Barry J
authors: BJ
authors: Everitt
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D016739:Behavior, Addictive / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003042:Cocaine / Q000009:adverse effects*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D011678:Punishment / Q000523:psychology; D051381:Rats; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D018765:Dopamine Uptake Inhibitors; D018490:Serotonin Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003042:Cocaine; D004298:Dopamine