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Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP).
Eur J Pharmacol. 1994 May 12; 257(1-2):27-38.EJ

Abstract

Rats were trained to discriminate the 5-HT receptor agonist m-chlorophenylpiperazine (mCPP; 1 mg/kg) from saline using a two-lever, water-reinforced drug discrimination task. The antidepressant trazodone (1-8 mg/kg), the 5-HT1B/2C receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP; 0.25-1 mg/kg) and MK 212 (0.125-1 mg/kg), and the mixed 5-HT1A/B receptor agonist RU 24969 (0.25-2 mg/kg) substituted fully for mCPP. The 5-HT2A/2C receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.25-1 mg/kg) and d-lysergic acid diethylamide (LSD; 0.02-0.08 mg/kg) and the 5-HT releaser fenfluramine (0.5-2 mg/kg) also mimicked mCPP. Agonists selective for the 5-HT1A or 5-HT3 receptor or the 5-HT reuptake site produced saline-lever responding. The ergoline derivative mesulergine (0.5-4 mg/kg) produced a partial agonist/antagonist profile. The 5-HT1/2 receptor antagonist metergoline (0.125-1 mg/kg) completely blocked the mCPP cue whereas the 5-HT2A/2C receptor antagonists ketanserin and LY 53857 as well as all other 5-HT receptor antagonists failed to block the mCPP cue. The dopamine receptor antagonists SCH 23390 and haloperidol were also ineffective mCPP antagonists. Following pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA; 100 mg/kg/day) for 3 consecutive days, the discriminability of low doses of mCPP increased, whereas the effects of fenfluramine decreased. The present results suggest that the discriminative stimulus effects of mCPP in rats are mediated primarily by postsynaptic 5-HT2C receptors.

Authors+Show Affiliations

University of Texas Medical Branch, Department of Pharmacology and Toxicology, Galveston 77555-1031.No affiliation info available

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

8082704

Citation

Callahan, P M., and K A. Cunningham. "Involvement of 5-HT2C Receptors in Mediating the Discriminative Stimulus Properties of M-chlorophenylpiperazine (mCPP)." European Journal of Pharmacology, vol. 257, no. 1-2, 1994, pp. 27-38.
Callahan PM, Cunningham KA. Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). Eur J Pharmacol. 1994;257(1-2):27-38.
Callahan, P. M., & Cunningham, K. A. (1994). Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). European Journal of Pharmacology, 257(1-2), 27-38.
Callahan PM, Cunningham KA. Involvement of 5-HT2C Receptors in Mediating the Discriminative Stimulus Properties of M-chlorophenylpiperazine (mCPP). Eur J Pharmacol. 1994 May 12;257(1-2):27-38. PubMed PMID: 8082704.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of 5-HT2C receptors in mediating the discriminative stimulus properties of m-chlorophenylpiperazine (mCPP). AU - Callahan,P M, AU - Cunningham,K A, PY - 1994/5/12/pubmed PY - 1994/5/12/medline PY - 1994/5/12/entrez SP - 27 EP - 38 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 257 IS - 1-2 N2 - Rats were trained to discriminate the 5-HT receptor agonist m-chlorophenylpiperazine (mCPP; 1 mg/kg) from saline using a two-lever, water-reinforced drug discrimination task. The antidepressant trazodone (1-8 mg/kg), the 5-HT1B/2C receptor agonists 1-(m-trifluoromethylphenyl)piperazine (TFMPP; 0.25-1 mg/kg) and MK 212 (0.125-1 mg/kg), and the mixed 5-HT1A/B receptor agonist RU 24969 (0.25-2 mg/kg) substituted fully for mCPP. The 5-HT2A/2C receptor agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 0.25-1 mg/kg) and d-lysergic acid diethylamide (LSD; 0.02-0.08 mg/kg) and the 5-HT releaser fenfluramine (0.5-2 mg/kg) also mimicked mCPP. Agonists selective for the 5-HT1A or 5-HT3 receptor or the 5-HT reuptake site produced saline-lever responding. The ergoline derivative mesulergine (0.5-4 mg/kg) produced a partial agonist/antagonist profile. The 5-HT1/2 receptor antagonist metergoline (0.125-1 mg/kg) completely blocked the mCPP cue whereas the 5-HT2A/2C receptor antagonists ketanserin and LY 53857 as well as all other 5-HT receptor antagonists failed to block the mCPP cue. The dopamine receptor antagonists SCH 23390 and haloperidol were also ineffective mCPP antagonists. Following pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA; 100 mg/kg/day) for 3 consecutive days, the discriminability of low doses of mCPP increased, whereas the effects of fenfluramine decreased. The present results suggest that the discriminative stimulus effects of mCPP in rats are mediated primarily by postsynaptic 5-HT2C receptors. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/8082704/Involvement_of_5_HT2C_receptors_in_mediating_the_discriminative_stimulus_properties_of_m_chlorophenylpiperazine__mCPP__ DB - PRIME DP - Unbound Medicine ER -