Possible 5-hydroxytryptamine1 (5-HT1) receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP).
Male rats (N = 24) were trained to discriminate 1-(m-trifluoromethylphenyl)piperazine (TFMPP) (0.8 mg/kg) from saline in a two-lever, drug discrimination situation. 5-Hydroxytryptamine (5-HT) agonists such as fenfluramine (0.8-1.6 mg/kg), m-chlorophenylpiperazine (0.1-1.6 mg/kg) and RU 24969 (0.1-1.6 mg/kg) mimicked TFMPP; 8-hydroxy-2-(di-n-propylamino)tetralin (0.02-0.32 mg/kg) and quipazine (0.2-3.2 mg/kg) elicited saline lever responding; d-lysergic acid diethylamide (0.1-0.16 mg/kg) produced intermediate results. The 5-HT antagonists BC 105 (1.6-12.8 mg/kg), bromolysergic diethylamide (0.8-1.28 mg/kg), ketanserin (0.8-6.4 mg/kg), Ly 53857 (0.2-1.6 mg/kg) and pirenperone (0.08-0.64 mg/kg) failed to attenuate the TFMPP cue; metergoline (0.4-6.4 mg/kg) and spiperone (0.08-1.28 mg/kg) decreased drug lever responding by as much as 60%. These data suggest that 5-HT agonists are not identical and that drug discrimination procedures can differentiate among them. Given that there is strong evidence to support the existence of heterogeneous 5-HT receptors, the present results also suggest that TFMPP acts through mechanism(s) similar to those of the novel 5-HT1 agonists m-chlorophenylpiperazine and RU 24969; these actions can be differentiated from those underlying d-lysergic acid diethylamide, quipazine and 2,5-dimethoxy-4-methylamphetamine, which are attenuated by putative 5-HT2 antagonists. Thus, the authors propose a role for 5-HT1 receptors in mediating the stimulus effects of TFMPP, although further research is necessary to identify functional antagonists of such systems.
D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D007211:Indoles; D010879:Piperazines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D008711:Metergoline; C018406:1-(3-trifluoromethylphenyl)piperazine; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D013134:Spiperone; C008340:mecoprop; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008238:Lysergic Acid Diethylamide; D008456:2-Methyl-4-chlorophenoxyacetic Acid