Coenzyme Q10 Suppression of Cue-related Reinstatement Through Cognition Improvement and Hippocampal Increase in BDNF Expression in Morphine-dependent Male Rats.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.