title: 5-HT6 antagonism attenuates cue-induced relapse to cocaine seeking without affecting cocaine reinforcement.
abstract: 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.
authors.affiliation: Neuroscience Research, GPRD, Abbott, Ludwigshafen, Germany. marcel.vangaalen@abbott.com
authors.forename: Marcel M
authors.initials: MM
authors.lastname: van Gaalen
authors.forename: Dustin
authors.initials: D
authors.lastname: Schetters
authors.forename: Anton N M
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: Taco J
authors.initials: TJ
authors.lastname: De Vries
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage* / Q000378:metabolism; D019970:Cocaine-Related Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D003463:Cues; D008297:Male; D011743:Pyrimidines / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D012008:Recurrence; D012054:Reinforcement, Psychology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D003042:Cocaine; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C114163:Ro 4-6790; D000096926:Benzenesulfonamides; C097216:serotonin 6 receptor; C117443:SB 271046