Peripheral electric stimulation attenuates the expression of cocaine-induced place preference in rats

The present study was designed to investigate the effect of peripheral electrical stimulation (PES), with high (100 Hz) or low (2 Hz) frequencies, on the expression of cocaine-induced conditioned place preference (CPP). Rats were trained with cocaine (0.1-10 mg/kg, i.p.) under a biased paradigm in a three-compartment chamber for the development of a CPP. One day following the last conditioning, the total time spent in each compartment was recorded after the deliverance of PES. Naloxone (1, 5, and 10 mg/kg, i.p.) was applied to investigate whether endogenous opioid receptor pathways play any role in the effect of PES. It was found that (1). 1 mg/kg and higher doses of cocaine, but not 0.5 mg/kg, produced significant place preference, (2). cocaine-induced CPP, once developed, maintained for more than 13 days in a cocaine-free state, (3). PES of 100 Hz, but not 2 Hz, significantly attenuated the expression of cocaine-induced CPP (P<0.01), (4). PES per se did not influence the natural place preference in rats, and (5). the inhibition of cocaine CPP induced by 100 Hz PES could be reversed by naloxone pre-treatment at 10 mg/kg, but not at lower doses. These results suggest that PES could inhibits cocaine-induced CPP in a frequency-dependent manner. This effect is probably mediated by an endogenous kappa-opioid mechanism.