Serotonin(2C) receptors appear to mediate genetic sensitivity to cocaine-induced convulsions

Rationale: C57BL/6ByJ (6ByJ) and C57BL/6J (6J) mice differ in their sensiti vity to cocaine-induced convulsions, with CD50 values being 100 and 70 mg/k g, respectively. This genetic sensitivity to cocaine-induced convulsions is probably related to 5-HT2 receptors, since the density of these sites and the concentration of 5-HT2 antagonists required to block cocaine-induced co nvulsions is lower in 6J mice relative to 6ByJ mice. Objective: Although 5- HT2 receptors appear to play a role in mediating genetic sensitivity to coc aine-induced convulsions, the role of 5-HT2 receptor subtypes in this effec t of cocaine has not been examined. Methods: The present study compared the effects of the preferential 5-HT2C agonists m-chlorophenylpiperazine (mCPP ) and 6-chloro-2-(1-piperazinyl)pyrazine (MK212) on cocaine-induced convuls ions in 6ByJ and 6J mice. General activity was also measured following pret reatment with mCPP and MK212. Results: Both mCPP and MK212 potentiated coca ine-induced convulsions and the effect of these agonists was more robust in 6ByJ mice relative to 6J mice. Conclusion: The findings from this study su pport previous research suggesting that 5-HT2 receptors play a role in medi ating cocaine-induced convulsions, and extend previous research by suggesti ng that the 5-HT2C receptor subtype mediates cocaine-induced convulsions an d genetic sensitivity to this toxic effect of cocaine.