Delayed aversive effects of high-dose fentanyl

The present study aimed to examine the effects of an acute administration of the μ-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 24 h 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.