Effects of the serotonin 5-HT2 antagonist, ritanserin, and the serotonin 5-HT1A antagonist, WAY 100635, on cocaine-seeking in rats

Manipulations of serotonergic systems have been shown to modify many of the behavioral effects of cocaine. It was recently demonstrated that serotonin (5-HT) depletions produced by inhibition of tryptophan hydroxylase reduced cocaine-seeking in an animal model. The present study was designed to dete rmine whether pretreatment with specific 5-HT antagonists might also decrea se cocaine-seeking. The effect of pretreatment with the 5-HT2 antagonist, r itanserin (0.0, 1.0, or 10.0 mg/kg), or the 5-HT1A antagonist, WAY 100635 ( 0.0, 0.1, 0.3, or 1.0 mg/kg), on cocaine (5.0, 10.0, or 20.0 mg/kg)-produce d reinstatement of extinguished drug-taking behavior was measured. Although ritanserin was ineffective, WAY 100635 attenuated cocaine-produced reinsta tement in a dose-dependent manner. These effects of WAY 100635 appeared to be specific since responding maintained by saccharin self-administration re mained high following pretreatment with 0.3 or 1.0 mg/kg WAY 100635. These data suggest a role of S-HT1A, but not 5-HT2, receptors in cocaine-seeking. (C) 2000 Elsevier Science Inc. All nights reserved.