Evidence that mCPP may have behavioural effects mediated by central 5‐HT1C receptors

Abstract

1 The effects of 1-(3-chlorophenyl)piperazine (mCPP) and 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP) on activity of rats in a novel cage, and on the rotorod and elevated bar co-ordination tests was examined. 2 Peripherally administered mCPP and TFMPP dose-dependently reduced locomotion, rearing, and feeding scores but not grooming of freely fed rats placed in a novel observation cage. Yawning behaviour was increased. Similar effects were also observed after injection of mCPP into the 3rd ventricle. 3 Co-ordination on a rotating drum of both untrained and trained rats was impaired following mCPP but co-ordination on an elevated bar was not. 4 The hypoactivity induced by mCPP was opposed by three antagonists with high affinity for the 5-hydroxytryptamine (5-HT_1C) site; metergoline, mianserin, cyproheptadine and possibly also by a fourth antagonist mesulergine. Metergoline, mianserin and cyproheptadine also opposed the reduction in feeding scores. However, neither effect of mCPP was antagonized by the 5-HT₂-receptor antagonists ketanserin or ritanserin, the 5-HT₃-receptor antagonist ICS 205–930, the 5-HT_1A and 5-HT_1B-receptor antagonists (—)-pindolol, (—)-propranolol and (±)-cyanopindolol or the 5-HT_1A-, 5-HT₂- and dopamine receptor antagonist spiperone. The specific α₂-adrenoceptor antagonist idazoxan was also without effect. 5 Hypoactivity induced by TFMPP was similarly antagonized by mianserin but unaffected by (±)-cyanopindolol. 6 These results suggest that the hypoactivity is mediated by central 5-HT_1C-receptors and that mCPP and possibly TFMPP may be 5-HT_1C-receptor agonists. 7 As mianserin, cyproheptadine and mesulergine in the absence of mCPP did not increase locomotion but increased the number of feeding scores, the activation of 5-HT_1C-receptors may be of physiological importance in the control of appetite. The possible relevance of these results to the therapeutic and side-effects of clinically used antidepressants (particularly trazodone and mianserin) and anorexigenic drugs is discussed.