Citalopram enhances cocaine's subjective effects in rats.
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.
Soto
Paul L
PL
Behavioral Biology Research Center, Johns Hopkins University, Baltimore, Maryland 21224-6823, USA. psoto@jhmi.edu
Hiranita
Takato
T
Katz
Jonathan L
JL
D000818:Animals; D015283:Citalopram / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D013045:Species Specificity
D015283:Citalopram; D003042:Cocaine; D017367:Selective Serotonin Reuptake Inhibitors