Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice

Melatonin has antioxidant and neuroprotective properties in human beings and experimental models, as well as ‘anti-estrogenic’ effects. Ethanol (EtOH) affects various behavioral parameters during a period known as ethanol-induced hangover. Our study evaluated the neuroprotective effect of melatonin on motor performance during ethanol hangover in male and female Swiss mice. The females were subjected to specific hormonal states: ovariectomized (OVX) and OVX estrogenized (OVX-E2). Mice received melatonin (25 μg/ml) or vehicle in their drinking water for seven days and were given intraperitoneal (i.p.) injections of EtOH (3.8 g/kg) or saline on the morning of the eighth day. Motor performance was evaluated by the tightrope test 6 h after EtOH exposure (hangover onset). During ethanol hangover, males exhibited lower motor performance than controls (p < 0.01) but pretreatment with melatonin significantly improved performance during hangover (p < 0.05). In females, melatonin treatment before ethanol-induced hangover led to a better motor performance in OVX compared with intact females (p < 0.01) and a lower performance in OVX-E2 compared with not-estrogenized OVX (p < 0.05). Consequently, estrogen reversed the motor performance enhancement afforded by melatonin. We conclude that estrogen interferes with the protective action of melatonin on motor performance during ethanol hangover.

► Exposure to melatonin improved the motor performance in male mice during hangover. ► Melatonin did not enhance motor performance in females during the hangover. ► Estrogens block the neuroprotective action of melatonin during ethanol hangover.