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Possible 5-hydroxytryptamine1 (5-HT1) receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP).
J Pharmacol Exp Ther. 1986 May; 237(2):369-77.JP

Abstract

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.

Authors

Cunningham KA
No affiliation info available
Appel JB
No affiliation info available

MeSH

2-Methyl-4-chlorophenoxyacetic Acid8-Hydroxy-2-(di-n-propylamino)tetralinAnimalsDiscrimination LearningDose-Response Relationship, DrugIndolesLysergic Acid DiethylamideMaleMetergolinePiperazinesRatsRats, Inbred StrainsReceptors, SerotoninSpiperoneTetrahydronaphthalenes

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2939233

Citation

Cunningham, K A., and J B. Appel. "Possible 5-hydroxytryptamine1 (5-HT1) Receptor Involvement in the Stimulus Properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP)." The Journal of Pharmacology and Experimental Therapeutics, vol. 237, no. 2, 1986, pp. 369-77.
Cunningham KA, Appel JB. Possible 5-hydroxytryptamine1 (5-HT1) receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP). J Pharmacol Exp Ther. 1986;237(2):369-77.
Cunningham, K. A., & Appel, J. B. (1986). Possible 5-hydroxytryptamine1 (5-HT1) receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP). The Journal of Pharmacology and Experimental Therapeutics, 237(2), 369-77.
Cunningham KA, Appel JB. Possible 5-hydroxytryptamine1 (5-HT1) Receptor Involvement in the Stimulus Properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP). J Pharmacol Exp Ther. 1986;237(2):369-77. PubMed PMID: 2939233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Possible 5-hydroxytryptamine1 (5-HT1) receptor involvement in the stimulus properties of 1-(m-trifluoromethylphenyl)piperazine (TFMPP). AU - Cunningham,K A, AU - Appel,J B, PY - 1986/5/1/pubmed PY - 1986/5/1/medline PY - 1986/5/1/entrez SP - 369 EP - 77 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 237 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2939233/Possible_5_hydroxytryptamine1__5_HT1__receptor_involvement_in_the_stimulus_properties_of_1__m_trifluoromethylphenyl_piperazine__TFMPP__ DB - PRIME DP - Unbound Medicine ER -