Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice

Abstract

Although systemic allopregnanolone (ALLO; a positive modulator of GABA(A) receptors) has been shown to enhance ethanol-reinforced responding and to modulate drinking patterns in rodents, the effects of centrally administered ALLO on ethanol intake are not known. The current work examined the effects of intracranial ALLO on operant ethanol self-administration in food- and water-satiated mice, with a procedure designed to estimate ALLO's influence on appetitive versus consummatory processes. Male C57BL/6J (B6) mice were trained to press an ethanol-appropriate lever by being reinforced with 30-min of continuous access to a 10% ethanol solution. Following surgical implantation of a guide cannula aimed at the lateral ventricle and subsequent habituation to vehicle infusions, ALLO (50-400 ng; ICV) was delivered immediately prior to session start. ALLO doses of 100 and 400 ng were further evaluated for their effects on locomotor behavior within activity chambers. ALLO selectively modulated ethanol intake patterns associated with the onset and maintenance of self-administration, while leaving appetitive (i.e., ethanol seeking) measures unaltered. The effects of ALLO on drinking patterns were dissociable from changes in locomotor behavior, as evidenced by the absence of ALLO's influence on response frequency and horizontal distance traveled. These findings support the premise that manipulations in brain ALLO levels may influence the regulatory processes governing ethanol consumption.

Fig. 1

Representative coronal brain section confirming guide cannulae placement into the lateral ventricle.

Fig. 2

The temporal distribution of licks following ICV ALLO. Cumulative records were compiled and collapsed for all mice and depicted in 10-min session intervals. Each bar represents the mean ± SEM of 17 mice. *p < 0.05, **p < 0.01 versus respective baseline (0 ng dose) values.

Fig. 3

The effects of ALLO (ICV) on locomotor activity. The total horizontal distance traveled (centimeters) is depicted for the entire 30-min test (panel A) and in 5-min epochs (panel B). Each bar represents the mean ± SEM of 7 mice.