Citalopram enhances cocaine's subjective effects in rats

Paul L. Soto, Takato Hiranita, Jonathan L. Katz

Research output: Contribution to journalArticlepeer-review

Abstract

Serotonin-selective reuptake inhibitors (SSRIs) have been shown to enhance the locomotor stimulatory, discriminative-stimulus, and convulsive effects of cocaine in rodents. A pharmacokinetic mechanism for the interaction is supported by increases in the brain levels of cocaine by fluoxetine treatment. Furthermore, the locomotor-stimulant effects of cocaine in rodents are enhanced by fluoxetine and fluvoxamine, SSRIs known to inhibit cocaine-metabolizing cytochrome P450 enzymes, whereas citalopram, an SSRI that does not inhibit P450 enzymes, does not enhance cocaine's locomotor-stimulant effects. Citalopram, however, attenuated the discriminative-stimulus effects of cocaine in squirrel monkeys trained to discriminate cocaine from saline, though it enhanced the discriminative-stimulus effects of a low dose of cocaine in rats trained to discriminate high and low doses of the drug. This study investigated the effects of citalopram on cocaine's discriminative-stimulus effects in rats trained more simply to discriminate cocaine from saline. Citalopram alone produced predominantly saline-appropriate responding, but when administered before cocaine, citalopram dose-dependently shifted the cocaine dose-response curve leftward. The present findings suggest that enhancement of cocaine's discriminative-stimulus effects may occur through a mechanism different from that underlying enhancement of cocaine's locomotor effects or that another action of citalopram selectively blocks locomotor enhancement.

Original languageEnglish (US)
Pages (from-to)759-762
Number of pages4
JournalBehavioural Pharmacology
Volume20
Issue number8
DOIs
StatePublished - Dec 2009

Keywords

  • Citalopram
  • Cocaine
  • Drug discrimination
  • Rats

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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