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Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5-HT2C receptors.
J Pharmacol Exp Ther. 1995 Sep; 274(3):1414-24.JP

Abstract

The present study assessed compounds displaying affinity for 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors for their ability to substitute for, enhance or antagonize the discriminative stimulus effects of cocaine (10 mg/kg) in rats. In substitution tests, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 0.2-1.6 mg/kg), the 5-HT1A/B receptor agonists RU 24969 (0.25-2 mg/kg) and CGS 12066B (2-16 mg/kg), the 5-HT1B/2C receptor agonists m-chlorophenylpiperazine (mCPP; 0.25-2 mg/kg) and m-trifluoromethylphenylpiperazine (TFMPP; 0.125-2 mg/kg), the 5-HT2A/2C receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane ([+/-]-DOB; 0.0625-0.5 mg/kg), the 5-HT2C receptor agonist MK 212 (0.25-1 mg/kg) and the nonselective 5-HT receptor agonist quipazine (1-8 mg/kg) engendered 30% to 70% cocaine-appropriate responding. The DA receptor antagonists SCH 23390 (0.025 or 0.05 mg/kg) and haloperidol (0.125 or 0.25 mg/kg) failed to block the partial substitution of RU 24969 (1 mg/kg) for cocaine. In combination tests, a fixed dose of either quipazine (4 mg/kg), RU 24969 (0.25, 0.5 or 1 mg/kg) or TFMPP (0.5 mg/kg) but not 8-OH-DPAT (0.4 mg/kg) or CGS 12066B (16 mg/kg) produced a leftward shift in the cocaine dose-response curve (0.625-5 mg/kg). In contrast, coadministration of either mCPP (0.25-2 mg/kg) or MK 212 (0.125-2 mg/kg) plus a dose of cocaine (5 mg/kg) that produced > 85% cocaine-appropriate responding when given alone partially antagonized cocaine; mCPP (1 mg/kg) also produced a rightward shift in the cocaine dose-response curve. Neither 8-OH-DPAT (0.2-1.6 mg/kg), (+/-)-DOB (0.125-0.5 mg/kg) nor quipazine (2-8 mg/kg) blocked the cocaine stimulus. The 5-HT1A receptor antagonist NAN 190 (0.2-0.8 mg/kg), the 5-HT2A/2C receptor antagonist LY 53857 (0.5-4 mg/kg) and the 5-HT/DA receptor antagonist pirenperone (0.5-4 mg/kg) neither substituted for nor enhanced cocaine; however, pirenperone but not NAN 190 or LY 53857 partially blocked the cocaine (10 mg/kg) response. Although 5-HT receptor compounds do not substitute for cocaine, several 5-HT receptor agonists (i.e., the indole derivative RU 24969 and the arylpiperazines mCPP, MK 212, TFMPP and quipazine), but not antagonists, differentially modulate the stimulus effects of cocaine.(

ABSTRACT

TRUNCATED AT 400 WORDS)

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Authors+Show Affiliations

Callahan PM
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, USA.
Cunningham KA
No affiliation info available

MeSH

AnimalsCocaineDiscrimination LearningDose-Response Relationship, DrugMaleNarcoticsRatsRats, Sprague-DawleyReceptor, Serotonin, 5-HT1BReceptor, Serotonin, 5-HT2CReceptors, SerotoninSerotonin AntagonistsSerotonin Receptor Agonists

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

7562516

Citation

Callahan, P M., and K A. Cunningham. "Modulation of the Discriminative Stimulus Properties of Cocaine By 5-HT1B and 5-HT2C Receptors." The Journal of Pharmacology and Experimental Therapeutics, vol. 274, no. 3, 1995, pp. 1414-24.
Callahan PM, Cunningham KA. Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5-HT2C receptors. J Pharmacol Exp Ther. 1995;274(3):1414-24.
Callahan, P. M., & Cunningham, K. A. (1995). Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5-HT2C receptors. The Journal of Pharmacology and Experimental Therapeutics, 274(3), 1414-24.
Callahan PM, Cunningham KA. Modulation of the Discriminative Stimulus Properties of Cocaine By 5-HT1B and 5-HT2C Receptors. J Pharmacol Exp Ther. 1995;274(3):1414-24. PubMed PMID: 7562516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of the discriminative stimulus properties of cocaine by 5-HT1B and 5-HT2C receptors. AU - Callahan,P M, AU - Cunningham,K A, PY - 1995/9/1/pubmed PY - 1995/9/1/medline PY - 1995/9/1/entrez SP - 1414 EP - 24 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 274 IS - 3 N2 - The present study assessed compounds displaying affinity for 5-HT1A, 5-HT1B, 5-HT2A and 5-HT2C receptors for their ability to substitute for, enhance or antagonize the discriminative stimulus effects of cocaine (10 mg/kg) in rats. In substitution tests, the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT; 0.2-1.6 mg/kg), the 5-HT1A/B receptor agonists RU 24969 (0.25-2 mg/kg) and CGS 12066B (2-16 mg/kg), the 5-HT1B/2C receptor agonists m-chlorophenylpiperazine (mCPP; 0.25-2 mg/kg) and m-trifluoromethylphenylpiperazine (TFMPP; 0.125-2 mg/kg), the 5-HT2A/2C receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane ([+/-]-DOB; 0.0625-0.5 mg/kg), the 5-HT2C receptor agonist MK 212 (0.25-1 mg/kg) and the nonselective 5-HT receptor agonist quipazine (1-8 mg/kg) engendered 30% to 70% cocaine-appropriate responding. The DA receptor antagonists SCH 23390 (0.025 or 0.05 mg/kg) and haloperidol (0.125 or 0.25 mg/kg) failed to block the partial substitution of RU 24969 (1 mg/kg) for cocaine. In combination tests, a fixed dose of either quipazine (4 mg/kg), RU 24969 (0.25, 0.5 or 1 mg/kg) or TFMPP (0.5 mg/kg) but not 8-OH-DPAT (0.4 mg/kg) or CGS 12066B (16 mg/kg) produced a leftward shift in the cocaine dose-response curve (0.625-5 mg/kg). In contrast, coadministration of either mCPP (0.25-2 mg/kg) or MK 212 (0.125-2 mg/kg) plus a dose of cocaine (5 mg/kg) that produced > 85% cocaine-appropriate responding when given alone partially antagonized cocaine; mCPP (1 mg/kg) also produced a rightward shift in the cocaine dose-response curve. Neither 8-OH-DPAT (0.2-1.6 mg/kg), (+/-)-DOB (0.125-0.5 mg/kg) nor quipazine (2-8 mg/kg) blocked the cocaine stimulus. The 5-HT1A receptor antagonist NAN 190 (0.2-0.8 mg/kg), the 5-HT2A/2C receptor antagonist LY 53857 (0.5-4 mg/kg) and the 5-HT/DA receptor antagonist pirenperone (0.5-4 mg/kg) neither substituted for nor enhanced cocaine; however, pirenperone but not NAN 190 or LY 53857 partially blocked the cocaine (10 mg/kg) response. Although 5-HT receptor compounds do not substitute for cocaine, several 5-HT receptor agonists (i.e., the indole derivative RU 24969 and the arylpiperazines mCPP, MK 212, TFMPP and quipazine), but not antagonists, differentially modulate the stimulus effects of cocaine.(ABSTRACT TRUNCATED AT 400 WORDS) SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7562516/Modulation_of_the_discriminative_stimulus_properties_of_cocaine_by_5_HT1B_and_5_HT2C_receptors_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7562516 DB - PRIME DP - Unbound Medicine ER -