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

Abstract

Introduction: Methamphetamine (METH) is a neurotoxic psychostimulant with highly addictive potential that leads to compulsive drug use and vulnerability to relapse. 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 (SC) administration of METH (0.125, 0.25, 0.5, 1, 2 and 4 mg/kg) could induce CPP and it was found that.METH with the 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 of the chronic stress during extinction phase, the animals were exposed to the restraint stress for one hour per day. Results: The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg..Based on the results, physical.stress.(restraint stress) whether 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 seems that exposure to the stress induces the relapse in abstinent amphetamine, but acute and chronic situation have a different reaction.

Keywords

• Reward
• Stress
• Methamphetamine (METH)
• Reinstatement
• Conditioned place preference