Potencies of antagonists indicate that 5-HT1C receptors mediate 1-3(chlorophenyl)piperazine-induced hypophagia.
1. 1-3(Chlorophenyl)piperazine (mCPP) (5 mg kg-1, i.p.) inhibited 2 h food intake in rats previously deprived of food for one day. Ten 5-hydroxytryptamine (5-HT) antagonists given s.c. opposed this hypophagic response. Calculated ID50 values correlated significantly with reported affinities (r = 0.81, n = 10, P less than 0.01) for 5-HT1C but not for 5-HT2, 5-HT1A, 5-HT1B or 5-HT1D receptors. 2. ID50 values of the ten antagonists against 5-hydroxytryptophan (5-HTP) + carbidopa-induced head shakes (a 5-HT2-mediated response) correlated significantly (r = 0.81, n = 10, P less than 0.01) with their affinities for 5-HT2 but not for 5-HT1A, 5-HT1B, 5-HT1C or 5-HT1D receptors. 3. ID50 values for inhibition of hypophagia and head shakes did not correlate significantly with each other. 4. Ratios of ID50 values against hypophagia and 5-HT2-mediated head shakes gave indices of relative in vivo potencies independent of differences in drug metabolism and disposition. These ratios correlated highly significantly (r = 0.91, n = 10, P less than 0.001) with the ratios of the affinities of the drugs for 5-HT1C (but not for 5-HT1A, 5-HT1B or 5-HT1B or 5-HT1D receptors) and with their affinities for 5-HT2 receptors. These results strongly support the hypothesis that mediation of mCPP-induced hypophagia is by stimulation of 5-HT1C receptors and the mediation of 5-HTP-induced head twitches by 5-HT2 receptors.
Kennett
G A
GA
Department of Neurochemistry, Institute of Neurology, Queen Square, London.
Curzon
G
G
D000818:Animals; D001066:Appetite / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C015068:1-(3-chlorophenyl)piperazine