Dissociation between the aversive and pharmacokinetic effects of ethanol in female Fischer and Lewis rats

National Institute on Alcohol Abuse and Alcoholism, Роквилл, Maryland, United States
Behavioural Brain Research (Impact Factor: 3.03). 09/2007; 182(1):51-6. DOI: 10.1016/j.bbr.2007.05.012
Source: PubMed


In humans and laboratory animal models, vulnerability to alcohol abuse is influenced by endogenous factors such as genotype. Using the inbred Fischer and Lewis rat strains, we previously reported stronger conditioned taste aversions (CTA) in male Fischer rats that could not be predicted by genotypic differences in alcohol absorption [Roma PG, Flint WW, Higley JD, Riley AL. Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats. Psychopharmacology (Berl) 2006;189:187-99]. The present study made similar assessments in Fischer and Lewis females via four-trial CTA induced by 1 or 1.5 g/kg intraperitoneal (IP) ethanol (n=10-12/strain/dose) as well as measures of blood alcohol concentrations (BAC) at 15, 60 and 180 min post-injection with 1.5 g/kg IP ethanol or saline (n=7-8/strain/dose). Dose-dependent CTAs were produced, but the strains did not differ from each other in these measures; however, BACs in the Lewis females were significantly higher than Fischer at all three time points. As with males of the Fischer and Lewis genotypes, a dissociation between BACs and the aversive effects of alcohol was observed. These data are the first assessments of these particular phenotypes in Fischer and Lewis females, and when considered with the historical data, suggest a Genotype x Sex interaction in the centrally mediated sensitivity to alcohol's aversive effects.

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    • "sensitive to ethanol reward (George, 1990, 1991; Suzuki et al., 1988) and less sensitive to the aversive effects of ethanol (Roma et al., 2006, 2007), relative to Fischer rats. Nevertheless, the present study appears to be the first to directly compare 24-h, free-choice ethanol intake between these two strains, and our finding that Lewis rats exhibit higher levels of voluntary ethanol intake than Fischer rats is consistent with a recent review concluding that genetic differences in 24-h intake are strongly positively correlated with operant responding for ethanol and negatively correlated with the magnitude of conditioned taste aversion to ethanol (Green and Grahame, 2008). "
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    ABSTRACT: Several lines of evidence implicate reciprocal interactions between excessive alcohol (ethanol) intake and dysregulation of circadian biological rhythms. Thus, chronic alcohol intake leads to widespread circadian disruption in both humans and experimental animals, while in turn, chronobiological disruption has been hypothesized to promote or sustain excessive alcohol intake. Nevertheless, the effects of circadian disruption on voluntary ethanol intake have not been investigated extensively, and prior studies have reported both increased and decreased ethanol intake in rats maintained under "shift-lag" lighting regimens mimicking those experienced by shift workers and transmeridian travelers. In the present study, male and female inbred Fischer and Lewis rats were housed in running wheel cages with continuous free-choice access to both water and 10% (vol/vol) ethanol solution and exposed to repeated 6-h phase advances of the daily light-dark (LD) cycle, whereas controls were kept under standard LD 12:12 conditions. Shift-lag lighting reduced overall ethanol and water intake, and reduced ethanol preference in Fischer rats. Although contrary to the hypothesis that circadian disruption would increase voluntary ethanol intake, these results are consistent with our previous report of reduced ethanol intake in selectively bred high-alcohol-drinking (HAD1) rats housed under a similar lighting regimen. We conclude that chronic circadian disruption is a form of chronobiological stressor that, like other stressors, can either increase or decrease ethanol intake, depending on a variety of poorly understood variables.
    Full-text · Article · May 2010 · Alcohol (Fayetteville, N.Y.)
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    • "Conditioned taste aversions (CTA) have also been described in adult rats using as the US an i.g. administration of 1.5 g/kg ethanol (Ciccocioppo et al., 1999), or with 2 g/kg injected i.p. (Ciccocioppo et al., 1999; Escarabajal et al., 2003; Roma et al., 2007). In infant rats ethanol has been also shown to be an effective aversive US for obtaining conditioned taste aversions (i.g., 1.2 g/kg, for example; (Hunt et al., 1990), or even texture aversions (2 or 2.5 g/kg; (Molina et al., 1996; Pautassi et al., 2005). "
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    ABSTRACT: Previous studies show that exposure to 1 or 2g/kg of ethanol during the last days of gestation increases ethanol acceptance in infant rats. We tested whether prenatal exposure to 3g/kg, a relatively high ethanol dose, generates an aversion to ethanol in both the dam and offspring, and whether this prenatal experience affects the expression of learning derived from ethanol exposure postnatally. The answer was uncertain, because postnatal administration of a 3-g/kg ethanol dose induces an aversion to ethanol after postnatal day (PD) 10 but increases ethanol acceptance when administered during the first postnatal week. In the present study, pregnant rats received intragastric administrations of water or ethanol (3g/kg) on gestation days 17-20. On PDs 7-8 or 10-11, the offspring were administered water or ethanol (3g/kg). Intake of ethanol and water, locomotor activity in an open field, and ethanol odor preference were evaluated in the pups, whereas the mothers were evaluated in terms of ethanol intake. Results indicated an aversion to ethanol in dams that had been administered ethanol during gestation, despite a general increase in ethanol intake observed in their pups relative to controls. The prenatal ethanol exposure also potentiated the increase in ethanol intake observed after intoxication on PDs 7-8. Ethanol intoxication on PDs 10-11 reduced ethanol consumption; this ethanol aversion was still evident in infant rats exposed prenatally to ethanol despite their general increase in ethanol intake. No effects of prenatal ethanol exposure were observed in terms of motor activity or odor preference. It is concluded that prenatal exposure to ethanol, even in a dose that induces ethanol aversion in the gestating dam, increases ethanol intake in infant rats and that this experience modulates age-related differences in subsequent postnatal learning about ethanol.
    Full-text · Article · Sep 2009 · Alcohol (Fayetteville, N.Y.)
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    • "The Lewis rats, then, may have exhibited smaller EtOH-induced suppression of CS intake in the Roma et al. (2006) study because they were less willing to forego fluid than were the Fischer rats. In a subsequent study comparing EtOH-induced suppression of CS intake in female Lewis and Fischer rats, the same group (Roma et al., 2007) reported no strain differences. "
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    ABSTRACT: Rats avoid intake of a palatable taste cue when paired with all drugs of abuse tested. Evidence suggests that, at least for morphine and cocaine, rats avoid the taste cue because they are anticipating the rewarding properties of the drug. Thus, the suppressive effects of a rewarding sucrose solution and cocaine, but not those of the putatively aversive agent, lithium chloride (LiCl), are exaggerated in drug-sensitive Lewis rats. Likewise, the suppressive effects of sucrose and morphine, but not those of LiCl, are eliminated by bilateral lesions of the gustatory thalamus. Unlike morphine and cocaine, it is less clear whether rewarding or aversive drug properties are responsible for ethanol-induced suppression of intake of a taste cue. The present set of studies tests whether, like cocaine, ethanol-induced suppression of intake of a taste cue also is greater in the drug-sensitive Lewis rats and whether the suppressive effects of the drug are prevented by bilateral lesions of the taste thalamus. In Experiment 1, fluid-deprived Lewis and Fischer rats were given 5-minute access to 0.15% saccharin and then injected with saline or a range of doses of ethanol (0.5, 0.75, 1.0, or 1.5 g/kg). There was a total of 6 such pairings. In Experiments 2 and 3, Sprague-Dawley rats received bilateral electrophysiologically guided lesions of the gustatory thalamus. After recovery, suppression of intake of the saccharin cue was evaluated following repeated daily pairings with either a high (1.5 g/kg) or a low (0.75 g/kg) dose of ethanol. Ethanol-induced suppression of intake of the saccharin conditioned stimulus (CS) did not differ between the drug-sensitive Lewis rats relative to the less-sensitive Fischer rats. Lesions of the taste thalamus, however, prevented the suppressive effect of the 0.75 g/kg dose of the drug, but had no impact on the suppressive effect of the 1.5 g/kg dose of ethanol. The results suggest that the suppressive effects of ethanol on CS intake are mediated by both rewarding and aversive consequences, varying as a function of dose.
    Preview · Article · Mar 2009 · Alcoholism Clinical and Experimental Research
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