Effects of Acute and Chronic Restraint Stress on Reinstatement of Extinguished Methamphetamine-Induced Conditioned Place Preference in Rats

Abstract

Environmental cues, such as drug exposure, peer influence and social stress, are the powerful triggers of drug relapse. In this study, we tried to find out the effect of acute and chronic restraint stress on reinstatement of extinguished METH-induced conditioned place preference (CPP) in rats.Methods: Subcutaneous (s.c.) administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP which dose of 0.5 mg/kg was more potent than other doses. In extinction phase, rats were put in the CPP box for 30 min per day for 8 consecutive days. After extinction, animals were exposed to restraint stress (3-h period, as an acute stress) 60 min before subcutaneous administration of ineffective dose of METH (0.125 mg/kg) in order to reinstate the extinguished METH-induced CPP. For induction the chronic stress during extinction phase animal exposed the restraint stress for a 1-h period/day. Results:The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg.Also result revealed that physical stress (restraint stress) acute and chronic can significantly induce reinstatement of METH-induced CPP (P˂0.001) in extinguished animals. Conclusion:Additionally, the chronic restraint stress could reduce duration of extinction (maintenance) of METH-induced CPP. It is supposed that exposure the stress induce the relapse in abstinent amphetamine, but acute and chronic situation have a different reaction.