Influence of cocaine history on the behavioral effects of dopamine D 3 receptor-selective compounds in monkeys

B. L. Blaylock, R. W. Gould, A. Banala, P. Grundt, R. R. Luedtke, A. H. Newman, M. A. Nader

Research output: Contribution to journalArticle

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Abstract

Although dopamine D3 receptors have been associated with cocaine abuse, little is known about the consequences of chronic cocaine on functional activity of D 3 receptor-preferring compounds. This study examined the behavioral effects of D 3 receptor-selective 4-phenylpiperazines with differing in vitro functional profiles in adult male rhesus monkeys with a history of cocaine self-administration and controls. In vitro assays found that PG 619 (N-(3-hydroxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl) benzamide HCl) was a potent D 3 antagonist in the mitogenesis assay, but a fully efficacious agonist in the adenylyl cyclase assay, NGB 2904 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide HCl) was a selective D 3 antagonist, whereas CJB 090 (N-(4-(4-(2,3- dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide HCl) exhibited a partial agonist profile in both in vitro assays. In behavioral studies, the D 3 preferential agonist quinpirole (0.03-1.0 mg/kg, i.v.) dose-dependently elicited yawns in both groups of monkeys. PG 619 and CJB 090 elicited yawns only in monkeys with an extensive history of cocaine, whereas NGB 2904 did not elicit yawns, but did antagonize quinpirole and PG 619-elicited yawning in cocaine-history monkeys. In another experiment, doses of PG 619 that elicited yawns did not alter response rates in monkeys self-administering cocaine (0.03-0.3 mg/kg per injection). Following saline extinction, cocaine (0.1 mg/kg) and quinpirole (0.1 mg/kg), but not PG 619 (0.1 mg/kg), reinstated cocaine-seeking behavior. When given before a cocaine prime, PG 619 decreased cocaine-elicited reinstatement. These findings suggest that (1) an incongruence between in vitro and in vivo assays, and (2) a history of cocaine self-administration can affect in vivo efficacy of D 3 receptor-preferring compounds PG 619 and CJB 090, which appear to be dependent on the behavioral assay.

Original languageEnglish (US)
Pages (from-to)1104-1113
Number of pages10
JournalNeuropsychopharmacology
Volume36
Issue number5
DOIs
StatePublished - Apr 2011

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Cocaine
Haplorhini
Dopamine
History
Quinpirole
Self Administration
Yawning
Dopamine D3 Receptors
Cocaine-Related Disorders
Macaca mulatta
Adenylyl Cyclases
Injections
N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridin-2-yl)benzamide
In Vitro Techniques

Keywords

  • addiction and substance abuse
  • cocaine
  • nonhuman primates
  • reinstatement
  • self-administration

Cite this

Influence of cocaine history on the behavioral effects of dopamine D 3 receptor-selective compounds in monkeys. / Blaylock, B. L.; Gould, R. W.; Banala, A.; Grundt, P.; Luedtke, R. R.; Newman, A. H.; Nader, M. A.

In: Neuropsychopharmacology, Vol. 36, No. 5, 04.2011, p. 1104-1113.

Research output: Contribution to journalArticle

Blaylock, B. L. ; Gould, R. W. ; Banala, A. ; Grundt, P. ; Luedtke, R. R. ; Newman, A. H. ; Nader, M. A. / Influence of cocaine history on the behavioral effects of dopamine D 3 receptor-selective compounds in monkeys. In: Neuropsychopharmacology. 2011 ; Vol. 36, No. 5. pp. 1104-1113.
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