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‐HT1C) 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‐HT1A and 5‐HT1B‐receptor antagonists (—)‐pindolol, (—)‐propranolol and (±)‐cyanopindolol or the 5‐HT1A‐, 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‐HT1C‐receptors and that mCPP and possibly TFMPP may be 5‐HT1C‐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‐HT1C‐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.
British Journal of Pharmacology – Wiley
Published: May 1, 1988
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