en Behavioral Neuroscience Behavioral Neuroscience Original Original <div style="text-align: justify;"><strong>Introduction</strong>: Opioid dependence significantly disrupts cognitive activities such as learning and memory, which may be the reason for a return to drug use. Morphine (MOR) can increase oxidative damage in the brain. We aim to investigate the effect of coenzyme Q10 (CoQ10) on cognitive impairment, cue-related reinstatement, and expression of brain-derived neurotrophic factor (BDNF) in MOR-dependent rats.<br> <strong>Methods</strong>: In this study, 40 male Wistar rats (200-220 g) were divided into 5 experimental groups (n=8) as follows: Oil group, MOR+oil group, MOR+CoQ10-100 group, MOR+CoQ10-200 group, and MOR+CoQ10-400 group. The rats were administered increasing doses of MOR (25 to 100 mg/kg, SC) once daily. After 21 days of addiction, CoQ10 treatment is administered by gavage at doses of 100, 200, and 400 mg/kg once daily for one month. CoQ10 is dissolved in 1 mL of sesame oil and administered. Behavioral assessments were performed using a novel object recognition (NOR) test, working memory in the Y-maze, social interaction, and conditioned place preference (CPP). The expression of BDNF was assessed in the hippocampus through immunohistochemistry.&nbsp;<br> <strong>Results</strong>: Treatment with CoQ10 at a dosage of 100, 200, and 400 mg/kg within 4 weeks resulted in a significant improvement in the NOR task (P<0.01, P<0.001), working memory in the Y-maze (P<0.01, P<0.001), social interaction (P<0.001), cue-related reinstatement in the CPP (P<0.01, P<0.001) and significantly increased expression of BDNF (P<0.001) in the hippocampus of male rats.<br> <strong>Conclusion</strong>: CoQ10 could improve cognitive impairment and reduce reinstatement in MOR-addicted male rats. Histologic examination confirmed the neuroprotective effects of CoQ10 in the hippocampus. CoQ10 could be a potential therapeutic agent for MOR-induced cognitive impairment and relapse.</div> Coenzyme Q10 (CoQ10), Cognitive dysfunction, Recurrence, Morphine (MOR), Opioid dependence 379 392 http://bcn.iums.ac.ir/browse.php?a_code=A-10-1425-7&slc_lang=en&sid=1 Somayeh Nazari snazari70@yahoo.com 13700319475328460053224 13700319475328460053224 No Student Research Committee, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Mobina Gheibi mobinagheibi78@gmail.com 13700319475328460053225 13700319475328460053225 No Student Research Committee, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Pouria Salehi Sangani salehipooria54@gmail.com 13700319475328460053226 13700319475328460053226 No Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Farzaneh Felehkari farzaneh.falekari@gmail.com 13700319475328460053227 0009-0004-3429-0162 No Student Research Committee, School of Allied Medical, Mazandaran University of Medical Sciences, Sari, Iran. Farnam Gohardehi fanamgohardehireseaech@gmail.com 13700319475328460053228 13700319475328460053228 No Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Saba Niknamfar sabaniknam45@gmail.com 13700319475328460053229 0009-0007-8364-4889 No Student Research Committee, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Hamid Jomehpour hjomehpour@yahoo.com 13700319475328460053230 13700319475328460053230 No Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. Hamed Ghazvini hghazvini1@gmail.com 13700319475328460053231 13700319475328460053231 No Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Seyedeh Masoumeh Seyedhosseini Tamijani seyedhoseini_sm@yahoo.com 13700319475328460053232 13700319475328460053232 No Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Vahabzadeh-Kebria Mohammad.Vahabzadeh.Kebria@yahoo.com 13700319475328460053233 0009-0007-9489-3784 No Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Fahimeh Mohseni fahime.mohseni123@gmail.com 13700319475328460053234 13700319475328460053234 No Center for Health Related Social and Behavioral Sciences Research, Shahroud University of Medical Sciences, Shahroud, Iran. Raheleh Rafaiee rahelerafaie@gmail.com 13700319475328460053235 13700319475328460053235 Yes Department of Neuroscience, School of Advanced Technologies in Medicine, Mazandaran University of Medical Sciences, Sari, Iran.