Delayed aversive effects of high-dose fentanyl. Prevention by a polyamine-deficient diet.

The present study aimed to examine the effects of an acute administration of the mu-opioid receptor fentanyl on affect as assessed by place-conditioning procedure in rats. We determined the affective properties of fentanyl not only immediately following its administration, but also 24h later. Experiments were performed using the dose of fentanyl (240 gamma/kg; four injections of 60 gamma/(ml kg) every 15 min, subcutaneously) for which secondary hyperalgesia has been previously described. Our results show that the acute administration of fentanyl display biphasic affective properties, with early rewarding and 24-h delayed aversive components. The 24-h delayed aversive effects of fentanyl were not observed in animals submitted to a polyamine-deficient diet, suggesting an NMDA-dependent mechanism.