Orexin gene expression is downregulated in alcohol dependent rats during acute alcohol withdrawal.

Alcohol use disorders (AUD) are chronic relapsing brain disorder characterized by compulsive and heavy alcohol consumption. During acute withdrawal, patients with AUD display excessive daytime sleepiness, a condition linked to serious life-threatening complications, however, the mechanism is not known. Orexin and melanin-concentrating hormone (MCH) are the two hypothalamic neuropeptides that regulate many behaviors including sleep-wakefulness, and alcohol consumption, reinforcement, and reinstatement. Importantly, loss of orexin neurons causes narcolepsy, a severe sleep disorder with excessive daytime sleepiness. Does acute alcohol withdrawal reduce orexin gene expression? To investigate this, male Sprague-Dawley rats were divided in two groups: Rats were either administered with alcohol, mixed with infant formula (alcohol group) or control mixture containing water and infant formula (Controls) by gastric intubation every 8 h for 4 days using Majchrowicz's chronic binge drinking protocol. The doses of alcohol were adjusted depending on degree of intoxication, exhibited by animals, prior to each dose. The animals were euthanized after 12 h of last alcohol/water administration. During withdrawal, the hypothalamus was rapidly dissected out, and the expressions of orexin and MCH genes were examined by Real-time PCR. There was a significant reduction in orexin gene expression in rats subjected to alcohol withdrawal as compared to controls. No such change was observed in the MCH gene expression. These results suggest that downregulation of orexin gene expression may be a possible mechanism responsible for excessive daytime sleepiness associated with alcohol withdrawal in patients with AUD.