William Le

Stress-Alcohol Behavioral Cross-Sensitization Is Dissociable from Biomolecular Indices of Glutamate Transmission

Faculty PI: Karen Szumlinski

Problematic alcohol use in women is often linked to coping with stress, yet most research examining stress and alcohol interactions has focused on males. This study determined whether repeated stress alters alcohol responsiveness differently in male and female mice, and the relationship between behavior and the expression of glutamate (an excitatory neurotransmitter)-related proteins linked to addiction. We hypothesized that stress would increase sensitivity to alcohol to a greater extent in females than in males, and that the magnitude of this stress-alcohol interaction would be related to elevated glutamate-related protein expression in a brain region called the nucleus accumbens. To test this, male and female mice underwent an 11-day unpredictable mild stress procedure. Mice were then tested for alcohol-induced locomotion (1 and 2 g/kg body weight) and sedation (5 g/kg). Three hours following 5 g/kg alcohol, nucleus accumbens tissue was collected and immunoblotted for glutamate receptors and related proteins. Stress reduced body weight, with females showing an earlier onset than males.  In both sexes, stress increased alcohol-induced locomotion and reduced alcohol’s sedative effects, indicating that stress increases the stimulatory effects of alcohol. Alcohol-injection differentially affected the expression of certain proteins in male versus female mice. Despite clear stress-alcohol behavioral cross-sensitization, we did not observe stress-alcohol interactions at the protein level in either sex. Although the functional relevance of the observed protein changes to behavioral cross-sensitization has yet to be elucidated, these findings suggest that the drivers of stress-alcohol behavioral interaction may differ between males and females.