The Effects of Testosterone on Cognitive Function Impairments and Brain Edema Induced by Methamphetamine in Gonadectomized Rats

Abstract

Background and purpose: Methamphetamine is one of the stimulant drugs that leads to the occurrence of cognitive and behavioral dysfunctions. Among the disorders that occur after methamphetamine abuse are learning and memory disorders as well as social interactions and anxiety. On the other hand, the function of sex steroids in the development of brain regions involved in reproduction has been the subject of extensive research over the years. In this context, testosterone plays an important role in neuronal and glial organization in prenatal and postnatal periods. Recent studies showed the effect of sex hormones on the nervous system and highlight the brain as a main target tissue for androgens. On the other hand, studies have shown that testosterone has neuroprotective effects against cognitive and behavioral disorders. Clinical manifestations of testosterone-related brain changes include cognitive impairments such as reduced memory efficiency related to the frontal cortex, as well as reduced long-term memory related to the hippocampus and other temporal regions of the midbrain. Androgens, especially testosterone, play an important role in memory function whereby the decrease and absence of testosterone leads to cognitive impairment and also neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. Therefore, in this study, the role of testosterone hormone in social memory, novel object recognition memory, as well as anxiety-like behavior and brain edema induced by a neurotoxic regimen of methamphetamine were investigated. Materials and methods: This study was conducted on 48 gonadectomized rats in 6 groups including control groups, methamphetamine (6mg/kg), solvent (sesame oil), methamphetamine + testosterone (0.25mg /kg), methamphetamine + testosterone (0.5 mg/kg) and methamphetamine + testosterone (1 mg/kg) were performed. At first, mice were anesthetized and gonadectomy surgery was performed. After 2 weeks of recovery, the evaluation of social memory was done using the three-chamber social interaction test, and anxiety-like behavior index using the open field test. Finally, the animals were killed and the brain tissue was evaluated for brain edema. Results: The findings of the study showed that social memory was significantly impaired in rats that received methamphetamine compared to the control group (P<0.001). On the other hand, results showed that there was a significant increase in anxiety-like behaviors as well as brain edema in rats that received methamphetamine (P<0.001). Statistical analysis also showed that the administration of testosterone hormone was able to improve cognitive functions and reduce anxiety-like behaviors and brain edema caused by methamphetamine (P<0.05). Conclusion: Overall, the present study suggests that the male sex hormone testosterone can be effective in improving behavioral disorders and anxiety, as well as brain edema caused by the administration of methamphetamine. Further research is needed to investigate the cellular and molecular mechanisms of the effects of this hormone.

Keywords

• methamphetamine
• testosterone
• anxiety
• brain edema
• social memory
• novel object memory