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Updated: May 20, 2026
A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in
Yann Pelloux1, Ruth Dilleen, Daina Economidou
1Behavioural and Clinical Neuroscience Institute and Department of Experimental Psychology, University of Cambridge, Cambridge, UK. yann.pelloux@univ-amu.fr
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.
