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Modulation of the discriminative stimulus properties of cocaine: comparison of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists.
Neuropharmacology. 1997 Mar; 36(3):373-81.N

Abstract

The present investigation examined the ability of serotonin (5-HT) agonists to substitute for, or alter (i.e. enhance or antagonize), the discriminative stimulus properties of a moderately low dose of cocaine (5 mg/kg) utilizing a two-lever, water-reinforced FR 20 drug discrimination procedure in rats. In substitution tests, the 5-HT1A receptor partial agonists buspirone and gepirone, the 5-HT1A/B receptor agonist RU 24969 and the 5-HT1B/2C receptor agonist m-trifluoromethyl-phenylpiperazine (TFMPP) failed to substitute for the cocaine stimulus, although RU 24969 did engender a maximum of 72% cocaine-lever responding. Fluoxetine (4 mg/kg) engendered primarily saline-appropriate responding. In combination tests, a fixed dose of either fluoxetine (4 mg/kg), RU 24969 (0.5 mg/kg) or TFMPP (0.5 mg/kg) produced a leftward shift in the cocaine dose-response curve (0.313-5 mg/kg). In contrast, buspirone (2.5-20 mg/kg) resulted in a dose-dependent attenuation (approximately 60% reduction) of the cocaine stimulus. Moreover, a dose of 10 mg/kg of buspirone co-administered with various doses of cocaine (1.25-10 mg/kg) engendered a rightward shift in the cocaine dose-response curve. Gepirone in combination with cocaine neither enhanced nor antagonized the cocaine discriminative stimulus. Whereas 5-HT agonists do not fully substitute for cocaine, the present results demonstrate that 5-HT1B, but not 5-HT1A, receptor agonists can modulate the discriminative stimulus properties of cocaine in a manner similar to that observed following administration of the 5-HT reuptake inhibitor fluoxetine. The ability of buspirone, but not gepirone, to attenuate the cocaine stimulus probably reflects its dopamine (DA) D2 receptor antagonist properties and not its efficacy at 5-HT1A receptors.

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Publisher Full Text

Authors+Show Affiliations

Callahan PM
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555, U.S.A.
Cunningham KA
No affiliation info available

MeSH

AnimalsBuspironeCocaineDiscrimination, PsychologicalDose-Response Relationship, DrugFluoxetineMaleRatsRats, Sprague-DawleySerotonin 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

9175616

Citation

Callahan, P M., and K A. Cunningham. "Modulation of the Discriminative Stimulus Properties of Cocaine: Comparison of the Effects of Fluoxetine With 5-HT1A and 5-HT1B Receptor Agonists." Neuropharmacology, vol. 36, no. 3, 1997, pp. 373-81.
Callahan PM, Cunningham KA. Modulation of the discriminative stimulus properties of cocaine: comparison of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists. Neuropharmacology. 1997;36(3):373-81.
Callahan, P. M., & Cunningham, K. A. (1997). Modulation of the discriminative stimulus properties of cocaine: comparison of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists. Neuropharmacology, 36(3), 373-81.
Callahan PM, Cunningham KA. Modulation of the Discriminative Stimulus Properties of Cocaine: Comparison of the Effects of Fluoxetine With 5-HT1A and 5-HT1B Receptor Agonists. Neuropharmacology. 1997;36(3):373-81. PubMed PMID: 9175616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of the discriminative stimulus properties of cocaine: comparison of the effects of fluoxetine with 5-HT1A and 5-HT1B receptor agonists. AU - Callahan,P M, AU - Cunningham,K A, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 373 EP - 81 JF - Neuropharmacology JO - Neuropharmacology VL - 36 IS - 3 N2 - The present investigation examined the ability of serotonin (5-HT) agonists to substitute for, or alter (i.e. enhance or antagonize), the discriminative stimulus properties of a moderately low dose of cocaine (5 mg/kg) utilizing a two-lever, water-reinforced FR 20 drug discrimination procedure in rats. In substitution tests, the 5-HT1A receptor partial agonists buspirone and gepirone, the 5-HT1A/B receptor agonist RU 24969 and the 5-HT1B/2C receptor agonist m-trifluoromethyl-phenylpiperazine (TFMPP) failed to substitute for the cocaine stimulus, although RU 24969 did engender a maximum of 72% cocaine-lever responding. Fluoxetine (4 mg/kg) engendered primarily saline-appropriate responding. In combination tests, a fixed dose of either fluoxetine (4 mg/kg), RU 24969 (0.5 mg/kg) or TFMPP (0.5 mg/kg) produced a leftward shift in the cocaine dose-response curve (0.313-5 mg/kg). In contrast, buspirone (2.5-20 mg/kg) resulted in a dose-dependent attenuation (approximately 60% reduction) of the cocaine stimulus. Moreover, a dose of 10 mg/kg of buspirone co-administered with various doses of cocaine (1.25-10 mg/kg) engendered a rightward shift in the cocaine dose-response curve. Gepirone in combination with cocaine neither enhanced nor antagonized the cocaine discriminative stimulus. Whereas 5-HT agonists do not fully substitute for cocaine, the present results demonstrate that 5-HT1B, but not 5-HT1A, receptor agonists can modulate the discriminative stimulus properties of cocaine in a manner similar to that observed following administration of the 5-HT reuptake inhibitor fluoxetine. The ability of buspirone, but not gepirone, to attenuate the cocaine stimulus probably reflects its dopamine (DA) D2 receptor antagonist properties and not its efficacy at 5-HT1A receptors. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/9175616/Modulation_of_the_discriminative_stimulus_properties_of_cocaine:_comparison_of_the_effects_of_fluoxetine_with_5_HT1A_and_5_HT1B_receptor_agonists_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028390897000105 DB - PRIME DP - Unbound Medicine ER -