The 5-HT2c receptors modulate both expression and extinction of cocaine-induced place preference in rats.
N.R. Capriles; S.J. Watson; H. Akil
Society for Neuroscience. 2010.
We previously demonstrated that the administration of the 5-HT2c antagonist SB242084 differentially modulates development and expression of conditioned place preference (CPP) in high responder (HR) and low-responder (LR) rats to novelty. This suggested that this receptor plays a key role in individual differences in cocaine reward and associated learning and memory processes. To further investigate the participation of the 5-HT2c receptors in memory consolidation, we compared the effects of different doses of the 5-HT2c antagonist SB242084 and the 5-HT2c agonist Ro 60-0175 on extinction of cocaine-induced CPP. Twenty-four hours after conditioning, HR and LR animals were injected with SB242084 (0, 0.25, 0.5 or 1 mg/kg, i.p.) or Ro 60-0175 (0, 0.3 or 1 mg/kg, i.p.), 30 and 20 min before Post-conditioning Test 1. Results showed that SB242084 and Ro 60-0175 produced opposite effects in the expression of cocaine-induced CPP. Moreover, HR animals were more responsive to low doses of these drugs, than the LR phenotype. On Post-conditioning Days 2-8, both HR and LR animals were given extinction trials by repeated CPP testing. At this time, same doses of SB242084, Ro 60-0175 or Vehicle were given immediately after the CPP tests. Results indicated that SB242084 prevented extinction of CPP, as compared to vehicle controls. On Post-conditioning Day 9, both HR and LR animals were challenged with a low dose of cocaine (10mg/kg, i.p.), and then tested for reinstatement of the CPP. Results showed that chronic treatment of the lower dose of Ro 60-0175 (0.3mg/kg, i.p.) prevented reinstatement in HR animals, as compared to vehicle. In addition, a similar trend was observed in LR animals after chronic treatment of a higher dose of Ro 60-0175 (1mg/kg, i.p.), suggesting once again that HR animals are more responsive to drugs affecting the 5-HT2c receptors. This is the first study investigating the contribution of the 5-HT2c receptors on extinction of cocaine-induced CPP. Overall, our results show that the 5-HT2c receptors contributes to the craving and relapse in cocaine-seeking behavior. Moreover, the mechanisms underlying this 5-HT2c receptor effects may be related to memory consolidation processes.