Abstract

Seeking opioids, even after a prolonged withdrawal period, is a main concern of opioid withdrawal. Resveratrol (RES) has been shown to exert inhibitory effects on glutamate release from cerebrocortical nerve terminals via N-methyl-D-aspartate (NMDA) antagonistic effects. In this study, the effects of RES on the acquisition and reinstatement of morphine were examined in a mouse model using the morphine-induced conditioned place preference (CPP) paradigm. In the first step, namely the acquisition phase, morphine was administered to mice for 4 consecutive days (daily 40 mg/kg, i.p. injection) and the mice were trained in a CPP chamber. In the second step, namely extinction and reinstatement, the animals underwent the same CPP training followed by extinction training on day 16 and reinstatement was investigated by CPP following the administration of a ‘reminding’ dose of morphine (10 mg/kg). Finally, the effects of RES (25, 50 and 75 mg/kg) on the acquisition and reinstatement induced by morphine were examined in a CPP test. Based on our data, RES (25, 50 and 75 mg/kg) reduced morphine tendency. In the second step of the experiment, after day 16 (following the ‘reminder’ dose of morphine at 10 mg/kg), the tendency of the animals for the white, drug-paired compartment of the CPP chamber significantly decreased following treatment with RES at 50 and 75 mg/kg (but not at 25 mg/kg). On the whole, the findings of this study demonstrate that RES decreases the acquisition and reinstatement of morphine-induced CPP in mice. © 2020 Spandidos Publications. All rights reserved.