Brain opioid-receptors are involved in mediating peripheral electric stimulation-induced inhibition of morphine conditioned place preference in rats

Conditioned place preference (CPP) paradigm has been suggested as one of the animal models for drug craving. The present study was performed to examine the effect of 100 Hz peripheral electric stimulation (PES) on the expression of morphine-induced CPP. Rats were trained with morphine for 4 days to establish the CPP paradigm in a three-chamber "unbiased" apparatus. Morphine-induced CPP was maintained up to 4 weeks when tests were given once a week. PES of 100 Hz administered 30 min a day for 3 days significantly attenuated morphine-induced CPP (P<0.01). I.c.v. injection of the delta-opioid receptor antagonist naltrindole (NTI) or the kappa-antagonist norbinaltorphimine (nor-BNI) but not the mu-antagonist cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), completely blocked the inhibitory effect of 100 Hz PES on the expression of morphine-induced CPP (P<0.05-0.01). These results indicate that the anti-craving effects induced by repeated PES of 100 Hz is mediated by the activation of supra-segmental delta- and kappa-opioid receptors in the central nervous system.