m-Chlorophenylpiperazine (mCPP) Modulates the Discriminative Stimulus Effects of Cocaine Through Actions at the 5-HT_2C Receptor

Agonists acting at the serotonin-1B receptor (5-HT_1BR) and 5-HT_2CR have been reported to potentiate and block, respectively, the discriminative stimulus effects of cocaine. The present investigation reassessed the antagonistic effects of the mixed 5-HT_2C/1BR agonist m-chlorophenylpiperazine (mCPP) on the discriminative stimulus effects of cocaine in the presence or absence of selective antagonism of the 5-HT _1BR or 5-HT_2CR. The stimulus effects of cocaine were attenuated by mCPP at doses that reduced response rates. The selective 5-HT _2CR antagonist SB 242084, but not the selective 5-HT_1BR antagonist GR 127935, reversed the mCPP-evoked attenuation of the cocaine cue and the suppression of response rates. These results demonstrate that the suppressive effects of mCPP on cocaine discrimination are related to stimulation of the 5-HT_2CR.