Journal
NEUROPSYCHOPHARMACOLOGY
Volume 37, Issue 11, Pages 2505-2514Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2012.111
Keywords
addiction; cocaine; compulsivity; punishment; serotonin; 5-HT2C receptors
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Funding
- United Kingdom Medical Research Council (MRC) Grant [G9536855]
- Medical Research Council [G1000183B, G0001354, G0001354B, G1002231] Funding Source: researchfish
- MRC [G1002231] Funding Source: UKRI
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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. Neuropsychopharmacology (2012) 37, 2505-2514; doi: 10.1038/npp.2012.111; published online 4 July 2012
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