Ketamine Differentially Attenuates Alcohol Intake in Male Versus Female Alcohol Preferring (P) Rats.

Abstract

Although various pharmacological tools in combating addiction to alcohol are available, their efficacy is limited. Hence, there is a critical need for development of more effective medications. Recent advances in the field have identified the glutamatergic system as a potential novel target for intervention in addictive behaviors. Hence, we evaluated the effects of acute administration of low (subanesthetic) doses of ketamine, an NMDA receptor antagonist, on alcohol intake and alcohol preference in both male and female rats. Adult alcohol preferring (P) rats were exposed to two-bottle choice (ethanol 10% and water) for at least three weeks following a nine-day training period and the effects of various doses of ketamine (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, injected subcutaneously, SC) on consumption of alcohol over various time periods during a 24 h interval were measured. Our results indicate that ketamine treatment significantly reduced both alcohol intake and preference in a time- and dose-dependent manner in both sexes. Moreover, a differential sensitivity between the sexes was observed. Thus, although alcohol intake was higher in males, female rats responded much more strongly to the highest dose of ketamine than males in the initial time periods. It is concluded that glutamatergic receptor manipulations may be of therapeutic potential in addiction to alcohol and that different sexes may respond differentially to such treatments.