5-HT6 antagonism attenuates cue-induced relapse to cocaine seeking without affecting cocaine reinforcement

M.M. Gaalen, D. Schetters, A.N.M. Schoffelmeer, T.J. de Vries

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Re-exposure to drug-related cues elicits drug-seeking behaviour and relapse in humans even after months of abstinence. Similarly, in laboratory rats, drug-associated stimuli reinstate cocaine seeking after prolonged withdrawal periods, thus providing a model to study mechanisms underlying cocaine relapse. 5-HT6 receptors (5-HT6Rs) are abundantly expressed in brain areas such as the nucleus accumbens and prefrontal cortex, which are critically involved in cocaine reinforcement and relapse. Nevertheless, the role of 5-HT6Rs in relapse mechanisms has not been investigated. We report here that the 5-HT6R antagonists SB-271046 and Ro-04-6790 significantly attenuate cue-induced cocaine seeking. However, effective doses of both 5-HT6R antagonists did not affect cocaine self-administration. This indicates that 5-HT6Rs are specifically involved in the secondary reinforcing properties of cocaine, leaving primary reinforcement and ability to perform an operant response unaffected. As such, 5-HT6Rs may represent a novel target for the prevention of relapse to cocaine seeking. © 2010 CINP.
Original languageEnglish
Pages (from-to)961-965
JournalInternational Journal of Neuropsychopharmacology
Issue number7
Publication statusPublished - 2010

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