en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction: </strong>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&nbsp; this&nbsp; study,&nbsp; we&nbsp; tried&nbsp; to&nbsp; find&nbsp; out&nbsp; the effect of acute and chronic restraint stress on reinstatement of extinguished METH-induced Conditioned Place&nbsp; Preference&nbsp; (CPP)&nbsp; in&nbsp; rats.&nbsp;<br> <strong>Methods:</strong> 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&nbsp; METH with the dose of 0.5 mg/kg was more potent than other doses. In&nbsp; extinction phase,&nbsp; rats&nbsp; were&nbsp; put&nbsp; in&nbsp; the&nbsp; CPP&nbsp; box&nbsp; for&nbsp; 30&nbsp; min&nbsp; per&nbsp; day&nbsp; for&nbsp; 8 consecutive days.&nbsp; After&nbsp; extinction,&nbsp; animals&nbsp; were&nbsp; exposed&nbsp; to restraint stress (3-h period, as an acute stress) 60&nbsp; min&nbsp; before&nbsp; subcutaneous&nbsp; administration&nbsp; of&nbsp; ineffective&nbsp; dose&nbsp; of&nbsp; METH&nbsp; (0.125&nbsp; mg/kg)&nbsp; in&nbsp; order&nbsp; to&nbsp; reinstate&nbsp; the&nbsp; extinguished&nbsp; 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.<br> <strong>Results: </strong>The results showed that the effective dose of METH to induce CPP was 0.5 mg/kg.&nbsp; Based on the results, physical&nbsp; stress&nbsp; (restraint stress) whether acute and chronic, can&nbsp; significantly&nbsp; induce&nbsp; reinstatement&nbsp; of METH-induced CPP (P˂0.001) in extinguished animals.&nbsp;<br> <strong>Conclusion:</strong> 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.&nbsp;</div> Reward, Stress, Methamphetamine (METH), Reinstatement, Conditioned place preference 157 166 http://bcn.iums.ac.ir/browse.php?a_code=A-10-107-2&slc_lang=en&sid=1 Zahra Taslimi za_t520@ymail.com 13700319475328460015596 13700319475328460015596 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Alireza Komaki alirezakomaki@yahoo.com 13700319475328460015597 13700319475328460015597 No Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Abbas Haghparast Haghparast@yahoo.com 13700319475328460015598 13700319475328460015598 No Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Abdolrahman Sarihi asarihi@yahoo.com 13700319475328460015599 13700319475328460015599 Yes Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.