Similar anxiety-like responses in male and female rats exposed to repeated withdrawals from ethanol

Abstract

Previous research indicated that male rats exhibited anxiety-like behavior following withdrawal from chronic ethanol exposure. This behavior, as well as other symptoms of withdrawal such as seizure susceptibility, may be sensitized in male rats repeatedly withdrawn from chronic ethanol exposure. Because there are sex differences in some alcohol effects, the present study explored whether male and female rats would respond differently to a course of repeated ethanol withdrawals. Similarly aged male and female rats were exposed to a control liquid diet or a diet containing ethanol (7% w/v). Ethanol-exposed rats had only one 5-day cycle of exposure or three cycles, with 2 days of control diet (CD) between cycles. At 5 h after the final ethanol was removed, the rats were placed as same-sexed pairs in the social interaction test; approximately half of the rats were tested later in the elevated plus maze. Rats withdrawn from ethanol after three cycles exhibited reduced the time spent in social interaction and general activity in the social interaction test and reduced the open and closed arm entries in the elevated plus maze. There were no sex differences in these effects. However, male rats exhibited a small anxiety-like response after one cycle of 5 days' exposure to ethanol and female rats did not. Thus, there are no sex differences in the three-cycle multiple-withdrawal paradigm, but there may be differences after briefer exposures.

Fig. 1

Social interaction behavior in male and female rats after exposure to CD or three cycles of 5 days of 7% ED. Pairs of rats with the same treatment and sex were tested in the arena for 5 min approximately 5 h after the ethanol was removed. The data represent the mean sec ± S.E.M. (upper panel) or line crosses (lower panel) for the 23 rats in each group. CD: control diet; ED: ethanol diet; M: male; F: female.

Fig. 2

Elevated plus maze behavior in male and female rats after exposure to control diet or three cycles of 5 days of 7% ED. Rats were tested in the maze for 5 min approximately 5 h after the ethanol was removed, immediately after completing the social interaction test. The data represent the mean number + S.E.M. of open (upper panel) or closed (lower panel) arm entries for 9 or 10 rats per group. CD: control diet; ED: ethanol diet; M: male; F: female.

Fig. 3

Social interaction behavior in male and female rats after exposure to CD or one cycle of 5 days of 7% ED. Pairs of rats with the same treatment and sex were tested in the arena for 5 min approximately 5 h after the ethanol was removed. The data represent the mean sec ± S.E.M. (upper panel) or line crosses (lower panel) for 23 rats in each group. Bars with different letters indicate significance group differences, P < .05, Tukey’s protected t test. CD: control diet; ED: ethanol diet; M: male; F: female.