PHARMACOLOGICAL EVALUATION OF THE DISCRIMINATIVE STIMULUS OF METACHLOROPHENYLPIPERAZINE

A pharmacologic analysis of the discriminative stimulus of metachlorop henylpiperazine (mCPP) is reported. mCPP and m-trifluoromethylphenylpi perazine generalised, whereas hoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)- 1H-indole, 6-chloro-2-(1-piperazinyl)-pyrazine, and mesulergine partia lly generalised to the mCPP discriminative cue. However, although mian serin, methiothepin, ritanserin, mesulergine and N-(1-methyl-5'-indoly l)-N'-(3-pyridyl)urea hydrochloride (SE 200646) all antagonised the ef fect of 5-hydroxytryptamine (5-HT) on IP3 formation in the rat choroid plexus, they failed to antagonise the mCPP response in the drug discr imination studies. The 5-HT3 receptor antagonist MDL 72222 neither gen eralised nor antagonised the mCPP cue. These data suggest that neither the 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT3, 5-HT5, 5-H T6, nor 5-HT7 receptors are involved. The response does appear to be m ediated by a postsynaptic 5-HT receptor, however, because fenfluramine generalised to the cue. Haloperidol generalises, and amphetamine part ially antagonises the mCPP discriminative cue and low doses of apomorp hine partially generalises to the mCPP cue, which suggests that a decr ease in dopamine neurotransmission may also be involved.