Adult anxiety-related behavior of rats following consumption during late adolescence of alcohol alone and in combination with caffeine

During late adolescence (postnatal days, PNDs, 45–55), male and female hooded rats were exposed to alcohol (1.14–1.33 g/kg/day), caffeine (27.03–27.22 mg/kg/day) or alcohol and caffeine together (1.20–1.34 g/kg/day alcohol plus 23.85–26.48 mg/kg/day caffeine) via their drinking water. The rats’ anxiety-related behavior was then assessed on reaching mid adulthood at PND120 in a light–dark box and an open field. For males only, alcohol alone led to increased entries of the light–dark box and (compared with water- or caffeine-exposed subjects) open-field rearing. Alcohol and caffeine combined also increased entries of the light–dark box light compartment and open-field ambulation for males only. The drug combination led to more male ambulation than for alcohol alone, and higher occupancy of the center squares of the apparatus than for males in any other group. Although alcohol alone had no subsequent effects on female behavior, alcohol and caffeine combined led to fewer entries of and less time spent in the light–dark box side then females in any other group. The drug combination also led to less female ambulation in the open field compared with either water- or caffeine-exposed females. The results were interpreted as sex-related potentiation by caffeine of alcohol’s developmental effects that resulted in lower levels of adult anxiety in male, but higher levels in females. The possible significance of this outcome for humans, especially females, was discussed.