PubMed · 15045746
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Sally Lehrman. 2004. Genetics. Sobering shift.. https://doi.org/10.1038/scientificamerican0404-22
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Repeated exposure to drugs of abuse results in an increased sensitivity to their behavioral effects, a phenomena referred to as behavioral sensitization. It has been suggested that the same neuroadaptations underlying behavioral sensitization contribute to the maintenance and reinstatement of addiction. Dysregulation of dopamine (DA) neurotransmission in the mesoaccumbens system is one neuroadaptation that is thought to lead to the compulsive drug-seeking that characterizes addiction. Evidence that sensitization to psychostimulants and opiates is associated with an enhancement of drug-evoked DA levels in the nucleus accumbens has also been obtained. Like other drugs of abuse, the acute administration of ethanol (ETOH) stimulates DA release in this brain region. Moreover, repeated ETOH experience results in an enhanced behavioral response to a subsequent ethanol challenge. Data regarding the influence of repeated ethanol intoxication and withdrawal upon mesoaccumbal DA neurotransmission is limited. Studies examining ETOH-evoked alterations in mesoaccumbal DA neurotransmission as a function of withdrawal duration are lacking. The present experiments quantified basal and ethanol-evoked DA levels 14 days and 24 h following the cessation of a repeated ETOH intoxication protocol, which results in sensitization to the locomotor activating effects of ethanol. Locomotor activity was assessed in parallel groups of animals. Studies were conducted in two mouse strains, C57BL/6J and DBA/2J, which differ in their behavioral responses to ETOH. The results indicate the development of transient tolerance to both ETOH-induced behavioral activation and evoked accumbens DA release at early withdrawal. Moreover, no enhanced DA response to a subsequent ETOH challenge could be demonstrated in ETOH experienced animals 2 weeks after withdrawal, in spite of the observation of clear behavioral sensitization at this time point. These results suggest that, at least in the case of ethanol, sensitization of the DA mesolimbic system may not be necessary for the development of behavioral sensitization.
AIMS: The cardio-protective effect of moderate alcohol consumption is partly mediated by HDL cholesterol. However, epidemiological studies suggest that binge drinking may not be associated with reduced risk of heart disease; a possible explanation is that the relationship of blood lipids with binge drinking is different from that with moderate intake. We investigated this hypothesis in a population study in three eastern European countries. METHODS: We conducted a cross-sectional study in random population samples in Novosibirsk (Russia), Krakow (Poland) and Karvina (Czech Republic). A sub-sample of 282 men aged 45-64 years who provided a fasting blood sample were analysed. Annual alcohol intake and the frequency of heavy binge drinking (> or =140 g of ethanol per session) were estimated from a graduated frequency questionnaire. RESULTS: Annual intake of alcohol was positively associated with total and HDL cholesterol. After controlling for annual intake, the frequency of heavy binge drinking was associated with increased concentrations of total and HDL cholesterol. By combining annual intake and drinking pattern, we found that men consuming >8 l of alcohol per year who had a heavy binge at least once a month had the mean total, HDL and LDL cholesterol 1.69 (SE 0.35), 0.61 (0.11) and 0.97 (0.34) mmol/l, respectively, higher than non-drinkers; this resulted in more favourable ratios of total and LDL cholesterol relative to HDL cholesterol in frequent heavy bingers. Triglycerides were not related to alcohol intake or binge drinking. CONCLUSIONS: Blood lipids do not seem to explain the apparent lack of the cardio-protective effect of binge drinking reported in epidemiological studies.
This study tested the hypothesis that a binge type of ethanol intake and ethanol withdrawal disturbs protein kinase C (PKC) homeostasis in a manner protected by 17beta-estradiol. Ovariectomized rats implanted with 17beta-estradiol or oil pellets received ethanol (7.5% weight/volume, 7 days) or control solution by a gavage method. The cerebelli were collected during ethanol exposure or ethanol withdrawal to assess the activity, protein levels, and cellular distribution of PKC(epsilon) and total PKC, using an ATP phosphorylation and immunoblot assays. While both ethanol exposure and ethanol withdrawal increased membrane protein levels and membrane translocation, only ethanol withdrawal enhanced activity of PKC(epsilon). Ethanol withdrawal not ethanol exposure increased the three parameters of total PKC. 17beta-Estradiol treatment prevented these changes in PKC profiles. These data suggest that an excessive episodic intake of ethanol followed by ethanol withdrawal disturbs PKC homeostasis and cellular distribution of PKC, in particular PKC(epsilon), in a manner that is protected by estrogen. PKC(epsilon) appears more vulnerable during ethanol withdrawal than during ethanol exposure.