Anxiogenic-like effects of mCPP and TFMPP in animal models are opposed by 5-HT1C receptor antagonists.

1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (0.1-1.0 mg/kg) reduce total interaction time in a rat social interaction test under low light familiar conditions and its following components; grooming, following, crawling over, fighting, sniffing. Locomotion was only reduced by the highest dose of mCPP. mCPP also reduced activity in the light but not total locomotion in a light/dark transition test. These results suggest that mCPP (and TFMPP) are anxiogenic but not sedative in these tests. The effect of mCPP on social interaction was blocked by three antagonists which share a high affinity for 5-HT1C and 5-HT2 receptors: mianserin, cyproheptadine and metergoline but not by the 5-HT2 antagonists ketanserin or ritanserin or the 5-HT1A and 5-HT1B antagonists cyanopindolol and (-)-propranolol. It was prevented by a low (0.05 mg/kg) but not by a high (1.0 mg/kg) dose of ICS 205,930 a specific 5-HT3 antagonist reported to be anxiolytic at low doses. It was also prevented by chronic pretreatment with the anxiolytic drug chlordiazepoxide. These results argue for an anxiogenic action of mCPP mediated by 5-HT1C receptors. Since the chronic chlordiazepoxide pretreatment did not prevent the hypolocomotion or hypophagia induced by mCPP at high dosage (5 mg/kg) these latter effects are unlikely to be secondary to anxiety.