Alcohol-induced brain pathology and behavioral dysfunction: Using an animal model to examine sex differences

Background: Human epidemiological studies suggest that the female brain may be more susceptible to the toxic effects of alcohol and that this is the reason why women show greater behavioral dysfunction after chronic alcohol exposure. This hypothesis was tested by using a rat model of chronic alcoholism [chronic ethanol treatment (CET)]. The investigation assessed sex differences in neuropathology and behavior after chronic exposure and subsequent withdrawal from alcohol. Methods: Young male and female rats (similar to 3 months old) were assigned to either a CET group, which received a 20% ethanol drinking solution for 20 weeks, or a pair-fed control group, which received ad libitum tap water and a restricted diet for 20 weeks. After the GET groups were phased off the 20% alcohol solution, learning and memory abilities were examined by using matching-to-position and nonmatching to-position tasks. Neuropathology was assessed in the frontal cortex and medial septal region. Results: CET was shown to cause behavioral deficits. The behavioral dysfunction was sex, task, and process dependent; i.e., GET-female rats displayed a delay-dependent impairment on delayed matching-to-position, whereas GET-male rats displayed a delay-independent impairment on delayed nonmatching-to-position. CET resulted in a significant reduction in the frontal cortical(FR1) and collosal thickness, as well as a decrease in cells staining immunopositive for choline acetyltransferase in the medial septal region. However, relative to male rats exposed to GET, female rats did not show any accelerated neuropathology after GET. Conclusions: Chronic exposure to ethanol does result in both brain and behavior dysfunction in male and female rats. The results demonstrate that different cognitive processes are altered by chronic ethanol exposure in male and female rats. However, the neurobiological mechanisms responsible for these differences remain to be determined.