Citalopram enhances cocaine's subjective effects in rats

Behav Pharmacol. 2009 Dec;20(8):759-62. doi: 10.1097/FBP.0b013e328333a267.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Citalopram / administration & dosage
  • Citalopram / metabolism
  • Citalopram / pharmacology*
  • Cocaine / administration & dosage
  • Cocaine / metabolism
  • Cocaine / pharmacology*
  • Conditioning, Operant / drug effects*
  • Discrimination Learning / drug effects*
  • Discrimination Learning / physiology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Male
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Uptake Inhibitors / administration & dosage
  • Serotonin Uptake Inhibitors / metabolism
  • Serotonin Uptake Inhibitors / pharmacology*
  • Species Specificity


  • Serotonin Uptake Inhibitors
  • Citalopram
  • Cocaine