Ethanol intake patterns in female C57BL/6J mice: Influence of allopregnanolone and the inhibition of its synthesis

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239-3098, USA.
Drug and Alcohol Dependence (Impact Factor: 3.42). 10/2008; 97(1-2):73-85. DOI: 10.1016/j.drugalcdep.2008.03.021
Source: PubMed


The neurosteroid allopregnanolone (ALLO) is a positive modulator of GABA(A) receptors that exhibits a psychopharmacological profile similar to ethanol (i.e., anxiolytic, sedative-hypnotic). Based on research suggesting that manipulation of ALLO levels altered ethanol self-administration in male rodents, the current studies determined whether exogenous ALLO administration or the inhibition of its synthesis in vivo modulated ethanol intake patterns in female C57BL/6J mice. Lickometer circuits collected temporal lick records of ethanol (10%, v/v) and water consumption during daily 2h limited access sessions. Following the establishment of stable ethanol intake, studies examined the effect of an acute ALLO challenge (3.2-24.0 mg/kg) or a 7-day blockade of ALLO production with finasteride (FIN; 50 or 100 mg/kg) on ethanol intake in a within-subjects design. In contrast to results in male mice, ethanol dose (g/kg), ethanol preference and most of the bout parameters were unaltered by ALLO pretreatment in female mice. Ethanol intake in females also was recalcitrant to 7-day treatment with 50 mg/kg FIN, whereas 100 mg/kg FIN significantly reduced the ethanol dose consumed by 35%. The FIN-attenuated ethanol intake was attributable to a significant decrease in bout frequency (up to 45%), with lick patterns indicating reduced maintenance of consumption throughout the 2-h session. FIN also produced a dose-dependent decrease in brain ALLO levels. In conjunction with data in male mice, the present findings indicate that there are sex differences in the physiological regulation of ethanol intake patterns by GABAergic neurosteroids.

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Available from: Matthew M Ford, Nov 25, 2014
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    • "For example, allopregnanolone administered systemically (Ford et al. 2005; Sinnott et al. 2002) or directly into the brain or ventricles (Finn et al. 2007; Janak and Gill 2003; Janak et al. 1998) altered alcohol self-administration in male rodents in a dose-dependent manner, with low doses increasing intake and higher doses reducing consumption. In contrast, female animals were relatively insensitive to this biphasic effect of allopregnanlone (Ford et al. 2008), possibly because they have higher basal levels of allopregnanolone (Finn et al. 2010). Finally, allopregnanolone can induce relapse-like behavior in mice (Finn et al. 2008) and rats (Nie and Janak 2003). "
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    • "Since the goal of these studies was to measure patterns of intake, we did not introduce the disruption of measuring blood ethanol concentration (BEC) during a particular hour post-injection. With limited access procedures, we have already shown that administration of ALLO and FIN did not alter ethanol metabolism, as the change in BEC corresponded to the change in ethanol intake in these studies (Ford et al., 2005a, 2005b, 2008a "
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