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Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action.
Psychopharmacology (Berl). 1998 Jun; 137(3):292-302.P

Abstract

Previous drug discrimination studies with the serotonergic drug m-chlorophenylpiperazine (mCPP) showed conflicting results, with some authors concluding that the cue was mediated by 5-HT2C receptors, but others that it was definitively not. We further examined the discriminative stimulus properties of mCPP in rats and reviewed previously published data. We trained rats to discriminate mCPP (2.0 mg/kg, PO) from water. We found that the mCPP cue generalized to m-trifluoromethyl-phenylpiperazine (TFMPP) and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and partially to eltoprazine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine and trazodone. A moderate level of generalization was obtained with quipazine, 1-(m-chlorophenyl)biguanide and clonidine. No generalization was found with flesinoxan, methiothepin, idazoxan and haloperidol. Mianserin and methysergide antagonized the mCPP stimulus, whereas ketanserin antagonized it partially. Metergoline, methiothepin and clozapine only marginally antagonized the mCPP stimulus. These results show that the discriminative stimulus effects of mCPP are predominantly mediated by 5-HT2C receptors, and to some extent by 5-HT1B receptors. When considering our results and other research together, the substitution tests clearly point to a 5-HT2C receptor mediated stimulus, with an additional role for 5-HT1B receptors. Antagonism studies are less clearcut, but are also suggestive of a 5-HT2C receptor mediated effect. A definitive answer as to whether other receptors, e.g. 5-HT2B and 5-HT7, are of any importance in mCPP's discriminative stimulus properties has to wait for more selective ligands.

Authors+Show Affiliations

Gommans J
Department of Psychopharmacology, Faculty of Pharmacy, Universiteit Utrecht, The Netherlands. J.Gommans@FAR.RUU.NL
Hijzen TH
No affiliation info available
Maes RA
No affiliation info available
Olivier B
No affiliation info available

MeSH

AnimalsBrainDiscrimination LearningGeneralization, StimulusMalePiperazinesRatsRats, WistarReceptor, Serotonin, 5-HT1BReceptor, Serotonin, 5-HT2CReceptors, SerotoninSerotonin Receptor Agonists

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

9683007

Citation

Gommans, J, et al. "Discriminative Stimulus Properties of mCPP: Evidence for a 5-HT2C Receptor Mode of Action." Psychopharmacology, vol. 137, no. 3, 1998, pp. 292-302.
Gommans J, Hijzen TH, Maes RA, et al. Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action. Psychopharmacology (Berl). 1998;137(3):292-302.
Gommans, J., Hijzen, T. H., Maes, R. A., & Olivier, B. (1998). Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action. Psychopharmacology, 137(3), 292-302.
Gommans J, et al. Discriminative Stimulus Properties of mCPP: Evidence for a 5-HT2C Receptor Mode of Action. Psychopharmacology (Berl). 1998;137(3):292-302. PubMed PMID: 9683007.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus properties of mCPP: evidence for a 5-HT2C receptor mode of action. AU - Gommans,J, AU - Hijzen,T H, AU - Maes,R A, AU - Olivier,B, PY - 1998/7/31/pubmed PY - 1998/7/31/medline PY - 1998/7/31/entrez SP - 292 EP - 302 JF - Psychopharmacology JO - Psychopharmacology (Berl) VL - 137 IS - 3 N2 - Previous drug discrimination studies with the serotonergic drug m-chlorophenylpiperazine (mCPP) showed conflicting results, with some authors concluding that the cue was mediated by 5-HT2C receptors, but others that it was definitively not. We further examined the discriminative stimulus properties of mCPP in rats and reviewed previously published data. We trained rats to discriminate mCPP (2.0 mg/kg, PO) from water. We found that the mCPP cue generalized to m-trifluoromethyl-phenylpiperazine (TFMPP) and 6-chloro-2-(1-piperazinyl)-pyrazine (MK-212), and partially to eltoprazine, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), fenfluramine and trazodone. A moderate level of generalization was obtained with quipazine, 1-(m-chlorophenyl)biguanide and clonidine. No generalization was found with flesinoxan, methiothepin, idazoxan and haloperidol. Mianserin and methysergide antagonized the mCPP stimulus, whereas ketanserin antagonized it partially. Metergoline, methiothepin and clozapine only marginally antagonized the mCPP stimulus. These results show that the discriminative stimulus effects of mCPP are predominantly mediated by 5-HT2C receptors, and to some extent by 5-HT1B receptors. When considering our results and other research together, the substitution tests clearly point to a 5-HT2C receptor mediated stimulus, with an additional role for 5-HT1B receptors. Antagonism studies are less clearcut, but are also suggestive of a 5-HT2C receptor mediated effect. A definitive answer as to whether other receptors, e.g. 5-HT2B and 5-HT7, are of any importance in mCPP's discriminative stimulus properties has to wait for more selective ligands. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/9683007/Discriminative_stimulus_properties_of_mCPP:_evidence_for_a_5_HT2C_receptor_mode_of_action_ DB - PRIME DP - Unbound Medicine ER -