Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats

Malgorzata Filip, Marcy J. Bubar, Kathryn Cunningham

Research output: Contribution to journalArticle

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Abstract

Rationale: The serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor (5-HT2R) family is an important regulator of the behavioral responsiveness to cocaine. Objective: The present study is an analysis of the role of the 5-HT2R subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in the discriminative stimulus effects of cocaine. Methods: Male Wistar rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task, and we investigated the ability of the 5-HT2AR antagonist 1(Z)-[2-(dimethylamino)ethoxyimino] -1(2-fluorophenyl)-3-(4-hydroxyphenyl)-2(E)-propene (SR 46349B), the 5-HT 2BR antagonist N-(1-methyl-5-indolyl)-N′-(3-methyl-5- isothiazolyl) urea (SB 204741), and the 5-HT2CR antagonist [(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo(1,7-bC)(2,6) naphthyridine (SDZ SER-082) to substitute for or to modulate the stimulus effects of cocaine. Results: Pretreatment with SR 46349B (0.5-1 mg/kg) resulted in a rightward shift of the cocaine dose-response curve, while SDZ SER-082 (1 mg/kg) shifted the dose-response for cocaine to the left; SB 204741 (1-3 mg/kg) was inactive. Conclusions: Our pharmacological analyses of selective antagonists of 5-HT2AR, 5-HT2BR, and 5-HT2CR indicate oppositional influence of 5-HT2AR and 5-HT2CR on the stimulus effects of cocaine and exclude a role for the 5-HT2BR. These data suggest that 5-HT2AR and 5-HT2CR may be important in modulating the subjective effects of cocaine in humans.

Original languageEnglish (US)
Pages (from-to)482-489
Number of pages8
JournalPsychopharmacology
Volume183
Issue number4
DOIs
StatePublished - Jan 2006

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Cocaine
Serotonin
Serotonin Antagonists
Wistar Rats
Pharmacology
Water

Keywords

  • Drug discrimination
  • SB 204741
  • SDZ SER-082
  • Serotonin receptors
  • SR 46349B

ASJC Scopus subject areas

  • Pharmacology

Cite this

Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats. / Filip, Malgorzata; Bubar, Marcy J.; Cunningham, Kathryn.

In: Psychopharmacology, Vol. 183, No. 4, 01.2006, p. 482-489.

Research output: Contribution to journalArticle

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abstract = "Rationale: The serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor (5-HT2R) family is an important regulator of the behavioral responsiveness to cocaine. Objective: The present study is an analysis of the role of the 5-HT2R subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in the discriminative stimulus effects of cocaine. Methods: Male Wistar rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task, and we investigated the ability of the 5-HT2AR antagonist 1(Z)-[2-(dimethylamino)ethoxyimino] -1(2-fluorophenyl)-3-(4-hydroxyphenyl)-2(E)-propene (SR 46349B), the 5-HT 2BR antagonist N-(1-methyl-5-indolyl)-N′-(3-methyl-5- isothiazolyl) urea (SB 204741), and the 5-HT2CR antagonist [(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo(1,7-bC)(2,6) naphthyridine (SDZ SER-082) to substitute for or to modulate the stimulus effects of cocaine. Results: Pretreatment with SR 46349B (0.5-1 mg/kg) resulted in a rightward shift of the cocaine dose-response curve, while SDZ SER-082 (1 mg/kg) shifted the dose-response for cocaine to the left; SB 204741 (1-3 mg/kg) was inactive. Conclusions: Our pharmacological analyses of selective antagonists of 5-HT2AR, 5-HT2BR, and 5-HT2CR indicate oppositional influence of 5-HT2AR and 5-HT2CR on the stimulus effects of cocaine and exclude a role for the 5-HT2BR. These data suggest that 5-HT2AR and 5-HT2CR may be important in modulating the subjective effects of cocaine in humans.",
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N2 - Rationale: The serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor (5-HT2R) family is an important regulator of the behavioral responsiveness to cocaine. Objective: The present study is an analysis of the role of the 5-HT2R subtypes (5-HT2AR, 5-HT2BR, and 5-HT2CR) in the discriminative stimulus effects of cocaine. Methods: Male Wistar rats were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced FR 20 task, and we investigated the ability of the 5-HT2AR antagonist 1(Z)-[2-(dimethylamino)ethoxyimino] -1(2-fluorophenyl)-3-(4-hydroxyphenyl)-2(E)-propene (SR 46349B), the 5-HT 2BR antagonist N-(1-methyl-5-indolyl)-N′-(3-methyl-5- isothiazolyl) urea (SB 204741), and the 5-HT2CR antagonist [(+)-cis-4,5,7a,8,9,10,11,11a-octahydro-7H-10-methylindolo(1,7-bC)(2,6) naphthyridine (SDZ SER-082) to substitute for or to modulate the stimulus effects of cocaine. Results: Pretreatment with SR 46349B (0.5-1 mg/kg) resulted in a rightward shift of the cocaine dose-response curve, while SDZ SER-082 (1 mg/kg) shifted the dose-response for cocaine to the left; SB 204741 (1-3 mg/kg) was inactive. Conclusions: Our pharmacological analyses of selective antagonists of 5-HT2AR, 5-HT2BR, and 5-HT2CR indicate oppositional influence of 5-HT2AR and 5-HT2CR on the stimulus effects of cocaine and exclude a role for the 5-HT2BR. These data suggest that 5-HT2AR and 5-HT2CR may be important in modulating the subjective effects of cocaine in humans.

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