Sex-Dependent Effects of Rivastigmine on Melatonin Receptors in Aged Rats

Abstract Objective Melatonin (5-methoxy-N-acetyltryptamine) is a hormone that is closely associated with other hormones and the circadian rhythm of organism. The prevalence of dementia is more significant in older people compared to the younger population. Rivastigmine (RIVA) is an inhibitor of acetylcholinesterase and butyrylcholinesterase, used therapeutically to alleviate several symptoms of dementia. While clinical and preclinical investigations have established the efficacy of RIVA on specific symptoms, its mechanism of action remains unclear. The objective of our research was to examine the impact of RIVA on memory and anxiety concerning the gene expression of melatonin receptors MT1 and MT2 in both 13-month-old male and female rats. Methods Twenty-four hours after a ten-day injection, Y-maze and elevated plus maze tests were conducted on each rat, after which they were decapitated for qPCR analysis. Results Our findings indicate that, based on Y-maze and elevated plus test parameters, RIVA enhanced exploratory behaviors in novel environments among female rats and induced anxiety-like behaviors in male rats relative to their female counterparts. Our results suggest that RIVA may have a gender-dependent influence on the development of new exploratory and anxiety-like behaviors in older individuals. The result indicates an essential interaction between cholinergic and melatonergic systems. Conclusion The effects of RIVA on memory and anxiety-like behaviors in aged rats may be cause changes in MT1 and MT2 gene expression. The variation in melatonin receptor expression across sexes indicates a potential gender-dependent impact in older populations.