Effects of fluoxetine and d-fenfluramine on cocaine-seeking behavior in rats.
BACKGROUND
Serotonin (5-HT) systems may play a role in modulating cocaine-seeking behavior.


OBJECTIVE
The present study examined the effects of acute administration of the 5-HT reuptake inhibitor (SRI) fluoxetine, and the SRI/releaser d-fenfluramine, on reinstatement of extinguished cocaine-seeking behavior elicited by either response-contingent presentations of cocaine-paired cues or cocaine priming.


METHODS
Separate groups of rats that had been trained to press a lever for a cocaine reinforcer (0.75 mg/kg per 0.1 ml, IV) with a light/tone stimulus complex paired with each infusion underwent daily extinction sessions during which responding had no scheduled consequences (i.e. neither cocaine nor the stimulus complex was available). Subsequently, the effects of fluoxetine (0-10.0 mg/kg, IP) on extinction and cue reinstatement of extinguished cocaine-seeking behavior were examined, as well as the effects of d-fenfluramine (0-3.0 mg/kg, IP) on cue reinstatement. Additionally, dose-dependent effects of fluoxetine (0-10.0 mg/kg, IP) and d-fenfluramine (0-1.0 mg/kg, IP) on cocaine-primed (0-15.0 mg/kg, IP) reinstatement of extinguished cocaine-seeking behavior were examined.


RESULTS
Fluoxetine dose-dependently attenuated cocaine-seeking behavior during extinction. Both fluoxetine and d-fenfluramine dose-dependently attenuated cue-reinstated cocaine-seeking behavior. In contrast, neither drug reliably altered cocaine-seeking behavior reinstated by cocaine priming.


CONCLUSIONS
These findings suggest that 5-HT indirect agonists effectively attenuate cocaine-seeking behavior elicited by cocaine-associated stimuli, but are much less effective in attenuating cocaine-seeking behavior elicited by cocaine priming.
Burmeister
Jeffrey J
JJ
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA.
Lungren
Erin M
EM
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA.
Neisewander
Janet L
JL
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, USA, USA. janet.neisewander@asu.edu.
D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy / Q000523:psychology; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005277:Fenfluramine / Q000494:pharmacology* / Q000627:therapeutic use; D005473:Fluoxetine / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology
D005473:Fluoxetine; D005277:Fenfluramine; D003042:Cocaine