TY - JOUR
T1 - 5-HT6 antagonism attenuates cue-induced relapse to cocaine seeking without affecting cocaine reinforcement
AU - Gaalen, M.M.
AU - Schetters, D.
AU - Schoffelmeer, A.N.M.
AU - de Vries, T.J.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1017/S1461145710000428
DO - 10.1017/S1461145710000428
M3 - Article
SN - 1461-1457
VL - 13
SP - 961
EP - 965
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
IS - 7
ER -
