Serum neurotransmitters level in response to acute restraint stress in perimenopausal female rats following L-arginine supplementation

Background: Reproductive aging in females is a continuous process involving progressive follicular depletion that begins at birth and extends through the menopausal transition. Objective: This study aimed to assess neurotransmitter interplay in L-arginine-supplemented perimenopausal female rats subjected to an acute restraint stress paradigm. Materials/Methods: Fifty-four female Sprague–Dawley rats were divided into three groups: Control rats (injected with Corn oil 2.5 μL/g BW); VCD rats (injected with 4-vinylcyclohexene diepoxide 160 mg/kg BW diluted in Corn oil) both for 15 days; and Aging rats (210 days old) left to age naturally. Sixty days after VCD/corn oil administration and 240 days in Aging group, rats were further divided into two subgroups: distilled water and L-arginine supplemented (100 mg/kg BW) for additional 30 days. At 130 days in Control and VCD groups, and 270 days in Aging group on diestrus morning, animals were decapitated at two different time points (“before” and “after”) restraint stress. Trunk blood was collected into plain tubes; centrifuged to extract serum which was stored at –80°C for dopamine, noradrenaline, and serotonin measurements using specialized high-sensitive ELISA kits from LDN immunoassay company, Germany). Results: Before and after restraint stress, serum dopamine and noradrenaline levels were significantly lower (P < 0.05) in the perimenopausal groups compared to Control group, whereas serum serotonin was not significantly different amongst the three groups. L-arginine supplementation after stress significantly reduced (P < 0.05) serum dopamine in VCD rats and significantly increased (P < 0.05) it in Aging rats. On the other hand, L-arginine supplementation significantly lowered (P < 0.05) serum noradrenaline in Control rats and significantly increased (P < 0.05) it in VCD rats. Furthermore, after stress, L-arginine supplementation also significantly lowered (P < 0.05) serum serotonin in VCD and Aging rats compared to the Control rats. Conclusion: L-arginine supplementation showed differential effects in an attempt to regulate neurotransmitters and this could be protective against hormonal fluctuations that occur during perimenopause.