Neuroprotective Effect of Rutin on Neurobehavioral Dysfunction and Cognitive Impairment-Induced by Methamphetamine in Male Rats

Background: Methamphetamine (MA) abuse is associated with neurobehavioral impairments, including antisocial behavior, anxiety, and cognitive deficits. Several studies have shown that rutin, a flavonoid compound, has neuroprotective effects against behavioral and memory disorders. Objectives: In this experimental study, the effects of pretreatment with rutin on social behavior, anxiety-related behavior, and cognitive dysfunction induced by MA were evaluated. Methods: Male Wistar rats were pretreated with intraventricular injection of three different doses of rutin (25, 50, or 150 nM) or saline 30 minutes prior to MA administration. Methamphetamine (4 × 4 mg/kg) or saline was administered subcutaneously at 2-hour intervals. Rectal temperature was measured 1 hour after the last MA administration. Behavioral and cognitive evaluations, encompassing open field, Y-maze, social interaction, and elevated plus-maze assessments, were performed three days subsequent to the final injection to assess locomotor activity, spatial working memory, sociability and social memory, as well as anxiety-related behaviors, respectively. Results: Methamphetamine induced hyperthermia (P < 0.001) and hyperlocomotion (P < 0.05) in rats compared to the control group. Although pretreatment with rutin reduced MA-induced hyperthermia and hyperlocomotion, this reduction was not statistically significant (P > 0.05). In addition, MA impaired working memory (P < 0.001) and increased anxiety-related behaviors (P < 0.001), while rutin improved working memory impairment (25 and 50 nM; P < 0.05 and P < 0.01, respectively) and reduced anxiety-related behaviors (50 and 150 nM; P < 0.001). Methamphetamine also induced social memory impairment (P < 0.001), while rutin (25, 50, and 150 nM; P < 0.001, P < 0.01, and P < 0.01, respectively) showed remarkable efficacy in ameliorating MA-induced social memory impairment. Sociability remained unchanged in the social interaction test. Our results also showed that the dose of 50 nM rutin performed better than doses of 25 and 100 nM in reducing MA-induced behavioral disturbances (P < 0.05). Conclusions: These findings suggest that rutin exerts a neuroprotective effect against MA-induced neurobehavioral and cognitive deficits. Therefore, rutin supplementation may be a promising therapeutic approach to mitigate MA-induced neurotoxicity.