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.

Effects of allopregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats

“…Results from the control conditions also agree with previous findings showing that ALLO did not decrease locomotor activity (Beauchamp et al 2000;Ford et al 2007) or responding maintained by sucrose (Sinnott et al 2002;Janak and Gill 2003). That ALLO significantly decreased cocaine-seeking behavior in females but not in males is consistent with results from a clinical study examining the influence of PROG on the attenuation of positive subjective ratings of cocaine in cocaine users (Evans and Foltin 2006).…”

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

“…Ethanol's ability to change local cellular levels of 3a,5a-THP in the NAc and CeA is particularly interesting, as these regions are strongly associated with ethanol reinforcement and consumption (Gonzales et al, 2004;McBride, 2002), and exogenous 3a,5a-THP has been shown to modulate ethanol self-administration. For example, several studies have shown that 3a,5a-THP alters ethanol consumption (Ford et al, 2007;Ford et al, 2005;Morrow et al, 2001) and reinforcement (Janak and Michael Gill, 2003;Janak et al, 1998). Ethanol-induced reductions of cellular 3a,5a-THP would most likely decrease GABA A receptor-mediated inhibition, which may alter activity of mesolimbic neurons and CeA circuitry involved in ethanol reinforcement.…”

The role of GABAA receptors in the development of alcoholism

“…It is therefore not surprising that sexually dimorphic effects have been noted in the interaction of ethanol and neurosteroids. ALLO pretreatment significantly increases voluntary ethanol consumption in male but not female mice (Sinnott et al, 2002) and intra-cranial injection of ALLO modulates the onset and maintenance of ethanol selfadministration but does not affect appetitive (ethanol seeking behaviors) (Ford et al, 2007).…”