Blocking serotonin 2A (5-HT2A) receptors attenuates the acquisition of methamphetamine-induced conditioned place preference in adult female rats

Abstract

Methamphetamine withdrawal can induce intense cravings leading to relapse. Contexts/cues paired with chronic methamphetamine use develop incentive motivational properties, promoting future drug-seeking and taking behavior. Research has shown that, in adult male rats, the selective 5-HT2A receptor antagonist M100907 attenuates the acquisition of methamphetamine-induced conditioned place preference (CPP), a measure that examines conditioned associations between the rewarding properties of drugs and contexts. However, these findings have not been extended to adult female rats. The present study investigated the effects of M100907 on the acquisition of methamphetamine-CPP in adult female rats. During conditioning, rats were administered M100907 (0, 0.025, 0.25\u2009mg/kg, i.p.) 15\u2009minutes before methamphetamine (1\u2009mg/kg, i.p.) and then placed into their initially non-preferred chamber for 30\u2009minutes, or administered saline and placed into their initially preferred chamber for 30\u2009minutes. Conditioning sessions were separated by four hours. Following four days of conditioning, the effects of M100907 on the acquisition of methamphetamine-CPP were assessed during a 15-minute drug-free test trial. Pretreatment with M100907 dose-dependently attenuated the acquisition of methamphetamine-induced CPP. Blocking 5-HT2A receptors with a low dose of the selective antagonist M100907 attenuated the rewarding effects of methamphetamine in adult female rats. These data provide further evidence that the 5-HT2A receptor subtype is involved in the behavioral effects of methamphetamine.