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

Melatonin (5-methoxy-N-acetyltryptamine) is closely linked to the body's natural circadian rhythm. Dementia is significantly more common among older individuals. Rivastigmine (RIVA) functions as a reversible inhibitor of acetylcholinesterase and butyrylcholinesterase, prescribed to help alleviate the symptoms of dementia. The mechanism behind RIVA's neuroendocrine interactions remains unclear despite its efficacy in treating specific symptoms. Our research aimed to investigate the effects of RIVA on memory, anxiety, and the expression of melatonin receptor genes MT1 and MT2 in middle-aged, 13-month-old male and female rats.

Rats were administered intraperitoneal injections of 2 mg/kg RIVA or saline once a day for ten days in succession. Twenty-four hours after the final injection, rats underwent the Y-maze and elevated plus maze tests, after which tissue samples were collected for qPCR analysis.

Behavioral tests revealed sex-specific responses; elevated plus maze test results indicated that RIVA did not alter exploratory behavior in female rats but decreased it in male rats compared to controls. At the same time, RIVA treatment resulted in significant decreases of MT1 and MT2 gene expression in the hippocampus of both sexes, but cortical expression showed different patterns in males and system.

RIVA treatment in middle-aged rats may cause changes in MT1 and MT2 gene expression concomitant with behavioral alterations. The variation in melatonin receptor expression across sexes indicates a potential sex-dependent impact in aging populations, suggesting an interaction between cholinergic and melatonergic systems.