Effects of Chronic Social Isolation Stress and Alcohol on the Reinforcing Properties of Ketamine in Male and Female Rats.
eNeuro March 1, 2025 Sarah D Jennings, Devin P Hagarty, Jordan Logue et al. 1 citation
Repeated ketamine infusions for depression may be riskier in people with a history of alcohol use, and effects differ by sex. In rats, females self-administered more ketamine than males. A history of alcohol increased ketamine intake in females, while a history of either isolation or alcohol independently increased ketamine intake in males. All groups showed similar extinction and cue-induced reinstatement. In the nucleus accumbens, isolation increased immature dendritic spines in males, an effect reduced by alcohol; alcohol increased immature spines in females. The findings suggest that prior social isolation and alcohol exposure alter ketamine's reinforcing properties in a sex-dependent manner, highlighting the need to consider sex and alcohol history when using ketamine to treat depression.