Ethanol intake patterns in female mice: influence of allopregnanolone and the inhibition of its synthesis - PubMed (original) (raw)

Ethanol intake patterns in female mice: influence of allopregnanolone and the inhibition of its synthesis

Matthew M Ford et al. Drug Alcohol Depend. 2008.

Abstract

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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Figures

Figure 1

Figure 1. Effects of exogenous ALLO challenge on the temporal distribution of ethanol (10E) licks

The frequency of 10E licks recorded throughout the 2-hr drinking session is depicted in 20-min bins (panel A). Lick patterns during the initial 20-min of access were further examined as 10-min intervals (panel B) to investigate consumption onset. A collapsed mean of the baseline days that immediately proceeded each ALLO test session is shown as 0 mg/kg. Vertical bars represent the mean ± SEM of licks for 24 mice. *P ≤ 0.05, **P ≤ 0.01 and ***P ≤ 0.001 versus within-subject baseline (i.e., 0 mg/kg) for the respective session interval.

Figure 2

Figure 2. Effects of sub-chronic FIN administration and its subsequent withdrawal on daily ethanol dose (g/kg) consumed

Two doses of FIN were assessed: 50 mg/kg (panel A) and 100 mg/kg (panel B). Each data point represents the mean ± SEM ethanol intake for 13–14 FIN-treated or 10 VEH-treated mice. *P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001 versus VEH-treated mice (i.e., 0 mg/kg) within a given drinking session.

Figure 3

Figure 3. Effects of FIN treatment (100 mg/kg) and withdrawal on the temporal distribution of ethanol (10E) licks

The frequency of 10E licks recorded throughout the 2-hr drinking session is depicted in 20-min bins (panel A). Lick patterns during the initial 20-min of access were further examined as 10-min intervals (panel B) to investigate consumption onset. Vertical bars represent the mean ± SEM of licks for 13 FIN-treated mice. *P ≤ 0.05, **P ≤ 0.01 and ***P ≤ 0.001 versus within-subject baseline for the respective session interval.

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