Alcoholism, clinical and experimental research
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Alcohol. Clin. Exp. Res. · Jun 2000
Reverse microdialysis of a dopamine uptake inhibitor in the nucleus accumbens of alcohol-preferring rats: effects on dialysate dopamine levels and ethanol intake.
The mesolimbic dopamine (DA) system has been implicated in mediating the reinforcing actions of ethanol (EtOH). This study examines the effects of local perfusion of the DA uptake inhibitor GBR12909 (GBR) on (1) DA levels in the nucleus accumbens (NAc) and (2) EtOH drinking in alcohol-preferring rats. ⋯ The results suggest (1) that EtOH drinking experience induces neuroadaptations that increase DA release in the NAc, and (2) that additional elevation in synaptic levels of DA in the NAc does not influence the maintenance of ongoing alcohol drinking under scheduled access conditions in alcohol-preferring animals.
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Alcohol. Clin. Exp. Res. · May 2000
Randomized Controlled Trial Clinical TrialCombining ondansetron and naltrexone effectively treats biologically predisposed alcoholics: from hypotheses to preliminary clinical evidence.
Individuals considered to be early onset alcoholics (EOA) are characterized by an early onset age, a broad range of antisocial behaviors, high familial loading, and presumed biological disease predisposition. Ondansetron, a 5-HT3 antagonist, improves drinking outcomes and increases abstinence rates among EOA. Individuals with high familial loading for developing alcoholism have lower levels of beta-endorphin and demonstrate a more pronounced increase in beta-endorphin levels in response to alcohol administration compared with individuals who do not have alcoholic relatives. The propensity for naltrexone (a mu opioid antagonist) to reduce alcohol's rewarding effects and drinking in humans is greatest in individuals with high familial loading. Predicated on the added knowledge that 5-HT3 receptors may themselves mediate alcohol reward via activation of the endogenous opioid system, we hypothesized that the combination of ondansetron and naltrexone would act synergistically and would be an effective treatment in EOA. ⋯ Ondansetron plus naltrexone seems to synergistically improve the drinking outcomes of EOA. Larger scale studies that test these medications, both alone and together, among various alcoholic subtypes are needed to establish and extend these promising findings.
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Alcohol. Clin. Exp. Res. · Apr 2000
Scanning electron microscopic studies on morphological abnormalities of erythrocytes in alcoholic liver diseases.
We previously reported that morphological abnormalities and the altered deformability of erythrocytes play important roles in disturbances of hepatic microcirculation associated with alcoholic liver disease. ⋯ The present study revealed that stomatocytes and acanthocytes are morphologically abnormal erythrocytes observed in the presence of alcoholic liver disease. These abnormal forms of erythrocytes tended to normalize as peripheral blood parameters and liver function were improved by abstinence, which suggests that erythrocyte morphology is related to the pathophysiology of alcoholic liver disease.
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Alcohol. Clin. Exp. Res. · Apr 2000
Involvement of dopamine D2 autoreceptors in the ventral tegmental area on alcohol and saccharin intake of the alcohol-preferring P rat.
The ventral tegmental area (VTA) dopamine (DA) system is considered to be involved in mediating the actions of ethanol (EtOH). The objective of the present study was to examine the role of VTA DA D2 receptors in regulating EtOH intake of alcohol-preferring P rats. ⋯ The data suggest that DA neuronal activity within the AVTA may be important for maintaining EtOH drinking in P rats, whereas DA neuronal activity within the PVTA may be involved in regulating general drinking and/or motivational behaviors. Overall, the results confirm the involvement of mesolimbic DA in EtOH self-administration and suggest that there is functional heterogeneity within the VTA regulating drinking behavior of the P rat.
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Alcohol. Clin. Exp. Res. · Jan 2000
Alcohol consumption, alcohol dependence, and all-cause mortality.
This study examined the effects of alcohol consumption and DSM-IV alcohol dependence on the risk of mortality. ⋯ Because alcohol dependence nullifies the protective effect of light and moderate drinking, it is important to understand its role as an independent risk factor for mortality. Differences between dependent and nondependent drinkers who drank comparable amounts suggest that this risk may result from longer and heavier drinking histories before baseline, more severe health problems at baseline, more heavy episodic drinking, and, possibly, differences in beverage preference.