Da. Baker et al., Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats, PSYCHOPHAR, 155(1), 2001, pp. 18-26
Rationale: Clinical studies examining the efficacy of the selective seroton
in reuptake inhibitor, fluoxetine. in decreasing craving and cocaine use ha
ve been inconsistent. Objective: To understand better the effects of fluoxe
tine treatment on incentive motivation for cocaine. the present study asses
sed the effects of chronic fluoxetine treatment on cocaine-seeking behavior
in rats following exposure to a cocaine self-administration environment or
a cocaine priming injection, Methods: Rats were trained to press a lever f
or a cocaine reinforcer (0.5 mg/kg per 0.1 ml, IV) or received yoked admini
stration of saline. They were then withdrawn from this regimen and given 20
daily injections of saline or fluoxetine (3.0 mg/kg, IP). Twenty-four hour
s after the last injection, the rats were placed in the self-administration
environment and cocaine-seeking behavior (i.e., non-reinforced lever press
ing) was measured for 90 min. Reinstatement of extinguished cocaine-seeking
behavior was then measured for 60 min following a saline injection and for
90 min following a cocaine priming injection (15 mg/kg, IP). Results: Chro
nic fluoxetine treatment attenuated cocaine-seeking behavior following expo
sure to the self-administration environment in most rats (n=16), but enhanc
ed cocaine-seeking behavior in two rats. Furthermore. the treatment failed
to alter cocaine-seeking behavior following a cocaine priming injection. In
terestingly, the amount of cocaine intake during self-administration traini
ng correlated with cocaine-seeking behavior following the cocaine priming i
njection. In fact, the priming injection reinstated cocaine-seeking behavio
r only in rats with high, but not low, cocaine intake based on a median spl
it. Conclusions: These results suggest that chronic fluoxetine treatment de
creases motivation for cocaine when animals are in a cocaine-free state. Fu
rthermore, individual differences in cocaine use are related to individual
differences in sensitivity to incentive motivational effects of cocaine pri
ming.