Discriminative stimulus properties of m-chlorophenylpiperazine.
Stimulus control was established in a group of 10 rats using a dose of m-chlorophenylpiperazine (MCPP) of 0.8 mg/kg, administered IP, 15 min before training. A two-lever operant task using a fixed-ratio 10 schedule of sweetened milk reinforcement was used. Based upon a criterion for the presence of stimulus control of five consecutive sessions during which 83% or more of all responses were on the appropriate lever, a mean of 27 sessions was required to reach criterion performance. Response rates were significantly suppressed by the training dose of MCPP (14 responses/min) as compared with saline sessions (38 responses/min). Subsequent to the establishment of stimulus control, tests of generalization were conducted with m-trifluoromethylphenylpiperazine (TFMPP), 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU-24969). MCPP generalized completely to MK-212 and TFMPP at doses of the latter drugs of 0.7 and 1.0 mg/kg, respectively. Maximum generalization to RU-24969 was 67% at a dose of 1.0 mg/kg but only 4 of 10 subjects completed the test session. The present results indicate that MCPP is efficacious as a discriminative stimulus. In addition, because of MCPP's relative selectivity for the 5-hydroxytryptamine c(5-HT1C) receptor subjects trained with MCPP may prove valuable in assessing the respective functional contributions of 5-HT1C sites to the actions of a variety of serotonergic agents.
Winter
J C
JC
Department of Pharmacology and Therapeutics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
Rabin
R A
RA
D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D005795:Generalization, Stimulus / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D007211:Indoles; D010879:Piperazines; D011719:Pyrazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; C014896:6-chloro-2-(1-piperazinyl)pyrazine; C015068:1-(3-chlorophenyl)piperazine