EVIDENCE THAT MCPP-INDUCED ANXIETY IN THE PLUS-MAZE IS MEDIATED BY POSTSYNAPTIC 5-HT2C RECEPTORS BUT NOT BY SYMPATHOMIMETIC EFFECTS

1-(3-Chlorophenyl)piperazine (mCPP) (0.125-1.0 mg/kg i.p.), previously shown to inhibit social interaction, dose-dependently reduced explora tion of the open arms of an elevated plus-maze. These findings suggest anxiogenic properties. The effect of mCPP was more potently inhibited by 1-(1-naphthyl)piperazine than by ketanserin, indicative of its med iation via activation of 5-HT2C rather than 5-HT2A receptors. The 5-HT 1B receptor agonist CGS 12066B did not antagonise the anxiety-like res ponse to mCPP, and further reduced exploration at the highest dose tes ted (10 mg/kg i.p.). Depletion of serotonin (5-HT) by p-chlorophenylal anine (PCPA, 150 mg/kg/day x 3) did not prevent the response, although PCPA itself increased open arm exploration. The 5-HT1A/B and beta-adr enoceptor antagonist 1-propanolol (5 mg/kg i.p.) and the peripheral be ta>(1)-receptor antagonist atenolol (20 mg/kg i.p.) showed no signific ant activity on the plus-maze either alone or against the anxiogenic e ffect of mCPP. These results indicate that mCPP induces anxiety in the rat in the elevated plus-maze primarily by stimulation of postsynapti c 5-HT2C receptors, and suggest that sympathomimetic effects of mCPP a re not involved.