Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice

Serotonin2C (5-HT2C) receptors have been implicated to treat mood disorders such as depression and anxiety. In the present study, the capacities of two 5-HT2C agonists, MK212 and mCPP, to produce conditioned taste aversions in mice were evaluated. On two training days, Swiss-Webster male mice (19-34 g) were trained to associate the flavor of a novel solution with the injection of various doses of MK212 or mCPP. On two alternate training days, mice were trained to associate a different flavored solution with an injection of saline. For testing, both flavored solutions were presented simultaneously and an avoidance of the MK212 or mCPP-paired solution indicated conditioned taste aversion. Robust conditioned taste aversions were observed to solutions paired with 1.0 or 10 mg/kg MK212 or mCPP. Acquisition of conditioned taste aversions was blocked by nonselective serotonin antagonists cyproheptadine, bromo-LSD, metergoline, methysergide and mianserin. Selective 5-HT2B/2C antagonist SB206,553 blocked both MK212- and mCPP-induced conditioned taste aversion although selective 5-HT2B/2C antagonist SB200,646 only blocked mCPP-induced conditioned taste aversion. In a single-bottle procedure, MK212, bromo-LSD, and mianserin failed to alter acquisition rate of a LiCl-induced conditioned taste aversion. Taken together, these data indicate that the serotonin agonists MK212 and mCPP produce conditioned taste aversion and that these effects are mediated predominantly through 5-HT2C receptors.