kl001 and Alcoholism

Metabolic dysfunction, mood disorders, anxiety disorders, and substance abuse disorders are associated with disruptions in circadian rhythm and circadian clock gene machinery. While the effects of alcohol on several core components of the clock genes have been described in rodent models, pharmacological activation or inhibition of clock gene functions has not been studied on alcohol drinking behaviors.. We investigated whether cryptochrome (CRY1/2) activator KL001 altered alcohol intake in mice in excessive and relapse-like alcohol drinking models.. Mice, subjected to 3 weeks of chronic intermittent alcohol drinking (IAD) (two-bottle choice, 24-h access every other day) developed excessive alcohol intake and high preference. We evaluated the pharmacological effects of KL001 after either 1-day acute withdrawal from IAD or 1-week chronic withdrawal using the alcohol deprivation effect (ADE) model.. Single pretreatment with KL001 at 1-4 mg kg. Pretreatment with KL001 (a CRY1/2 activator) reduces excessive and "relapse" alcohol drinking in mice. Our in vivo results with a CRY activator suggest a possible novel target for alcohol treatment intervention.

Topics: Alcohol Drinking; Alcoholism; Animals; Carbazoles; Central Nervous System Depressants; Cryptochromes; Dose-Response Relationship, Drug; Drug Tolerance; Enzyme Activation; Ethanol; Male; Mice; Mice, Inbred C57BL; Recurrence; Substance Withdrawal Syndrome; Sulfonamides