Monoamine reuptake inhibitors enhance the discriminative state induced by cocaine in the rat

Kathryn Cunningham, Patrick M. Callahan

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Cocaine inhibits the reuptake of dopamine (DA), norepinephrine (NE), and serotonin (5-HT). To investigate the relative role of such reuptake processes in the discriminative stimulus properties of cocaine, male rats (N=16) were trained to discriminate cocaine (10 mg/kg) from saline in a two-lever, water-reinforced drug discrimination task and were administered neuroactive compounds during substitution or combination tests. The DA reuptake inhibitor GBR 12909 (2-16 mg/kg) completely mimicked cocaine. The reuptake inhibitors for NE (desipramine; 2-8 mg/kg) and 5-HT (fluoxetine; 0.625-5 mg/kg) did not substitute for the training drug. A low dose of either desipramine (3 mg/kg), fluoxetine (1.25 mg/kg), or GBR 12909 (2 mg/kg) coadministered with low doses of cocaine (0.625-2.5 mg/kg) enhanced the discriminative stimulus properties of this psychostimulant. The dose predicted to elicit 50% drug-lever responding is reduced (ED50) in the presence of desipramine (0.38 mg/kg), fluoxetine (0.79 mg/kg) or GBR 12909 (0.84 mg/kg) compared to the ED50 for cocaine (1.57 mg/kg) in the absence of any reuptake inhibitor. The finding that GBR 12909 mimics the cocaine cue corroborates the hypothesis that the stimulus properties of cocaine are mediated predominantly by DA systems. The potentiation of the stimulus effects of cocaine by monoamine reuptake inhibitors in rats suggests that these drugs could also amplify the subjective effects of cocaine in humans, a possibility that should be considered given the current use of antidepressants in the treatment of cocaine abusers.

Original languageEnglish (US)
Pages (from-to)177-180
Number of pages4
JournalPsychopharmacology
Volume104
Issue number2
DOIs
StatePublished - Jun 1991

Fingerprint

Cocaine
Desipramine
Fluoxetine
Serotonin
Pharmaceutical Preparations
Dopamine
Norepinephrine
Dopamine Uptake Inhibitors
Antidepressive Agents
Cues
vanoxerine
Water

Keywords

  • Cocaine
  • Dopamine
  • Drug discrimination
  • Reuptake inhibition
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Monoamine reuptake inhibitors enhance the discriminative state induced by cocaine in the rat. / Cunningham, Kathryn; Callahan, Patrick M.

In: Psychopharmacology, Vol. 104, No. 2, 06.1991, p. 177-180.

Research output: Contribution to journalArticle

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