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

Abstract

Background: 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.

Purpose: 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.

Study design: 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.

Results: 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.

Conclusion: 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.

Keywords: NMDA receptor; alcohol intake; alcohol preference; alcohol use disorders; glutamate receptors; sex differences.

Figure 1

Effects of various doses of ketamine on (a) alcohol consumption (g/kg/h) and (b) percent alcohol preference [alcohol volume/(alcohol volume + water volume) × 100], during the 24-hour test (broken into various time periods) in alcohol preferring (P) rats. Both sexes are combined. Ketamine was injected SC 15 min before alcohol exposure. Values are mean ±SEM. N = 8 male and 10 female rats.

Figure 2

Effects of various doses of ketamine on (a) alcohol consumption (g/kg/h) and (b) percent alcohol preference [alcohol volume/(alcohol volume + water volume) × 100], during the 24-hour test (broken into various time periods) in male and female alcohol preferring (P) rats. Ketamine was injected SC 15 min before alcohol exposure. Values are mean ±SEM. N = 8 male and 10 female rats.