FETAL ETHANOL EFFECTS ON BENZODIAZEPINE SENSITIVITY MEASURED BY BEHAVIOR ON THE ELEVATED PLUS-MAZE

Rodents prenatally exposed to ethanol demonstrate altered behavioral a nd hormonal responses to stressful environments. Prenatal ethanol expo sure may also have long-term effects on the offspring's GABAergic syst em. Using the elevated plus-maze, the present study examined the sensi tivity of adult Sprague-Dawley rat offspring from prenatal ethanol (E) , pair-fed (PF) and ad lib-fed control (C) conditions to the effects o f benzodiazepine (BZD) on plus-maze behavior and corticosterone (CORT) responses. At 60-90 days of age, E, PF, and C males and females were injected subcutaneously with either BZD or saline. Twenty minutes late r animals were placed in an open field (OF) for a 5-min test and then on the plus-maze for a 5 min test; behaviors were recorded during test ing and blood samples collected at the end of testing for CORT determi nations. Overall, sex differences were observed in both OF and plus-ma ze behaviors. Females showed more ambulation and rearing in the OF tha n males, and exhibited increased exploratory behaviors and decreased f ear-related behaviors compared to males an the plus-maze. Following BZ D treatment, both males and females exhibited increased time on open a rms, increased open arm entries, and decreased time on closed arms com pared to saline-treated males and females, regardless of prenatal trea tment. These differences did not appear to be due to altered activity levels, as BZD treatment had no effect on total ambulation in the OF. Importantly, although no significant differences in plus-maze behavior s were found among saline-injected E, PF, and C males or females, BZD treatment differentially affected E males and females compared to thei r PF and C counterparts. Both E males and females treated with BZD spe nt increased time on open arms and decreased time on closed arms compa red to their PF and C counterparts, suggesting decreased fear. Further , BZD-treated E males exhibited decreased open and closed arm entries, spent significantly more time in the central area, and had lower CORT levels, another index of fear or stress, compared to BZD-treated PF a nd C males. These data support and extend previous work demonstrating that the plus-maze provides a reliable measure of anxiety/fear, and th at plus-maze behavior is sensitive to anxiolytic agents such as BZD. F urthermore, these data suggest that prenatal ethanol exposure may alte r sensitivity to the effects of BZD on plus-maze behavior and CORT res ponsiveness, and may do so differentially in male and females offsprin g. (C) 1998 Elsevier Science Inc.