Multiphasic Consequences of the Acute Administration of Ethanol on Cerebral Glucose Metabolism in the Rat
ABSTRACT The present study investigated the role of the postinjection interval in determining the functional consequences of acute ethanol administration in the CNS. Local cerebral metabolic rates for glucose (LCMRglc) were determined by the 2[14C]deoxyglucose method in 48 brain structures of ethanol-naive Sprague–Dawley rats. Tracer was injected 1 or 45 min after a 0.8 g/kg intragastric dose of ethanol or water. At the early time point, LCMRglc was increased in a highly restricted portion of the basal ganglia that included the dorsal striatum, globus pallidus, and core of the nucleus accumbens, compared to water controls. No significant decreases were found at this early time point. At the later time point, by contrast, LCMRglc was decreased in a different set of brain structures. These sites were limbic in nature and included the infralimbic and anterior cingulate cortices, dentate gyrus, lateral septum, and the bed nucleus of the stria terminalis. These data indicate that there are multiple phases that can be detected during the time course of an acute dose of ethanol. They further demonstrate the involvement of different neural systems at the two time points. Increased activity in basal ganglia is consistent with stimulated motor activity, whereas diminished activity in limbic sites may correspond to changes in mood and motivation.
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ABSTRACT: Near the end of the second postnatal week motor activity is increased soon after ethanol administration (2.5 g/kg) while sedation-like effects prevail when blood ethanol levels reach peak values. This time course coincides with biphasic reinforcement (appetitive and aversive) effects of ethanol determined at the same age. The present experiments tested the hypothesis that ethanol-induced activity during early development in the rat depends on the dopamine system, which is functional in modulating motor activity early in ontogeny. Experiments 1a and 1b tested ethanol-induced activity (0 or 2.5 g/kg) after a D1-like (SCH23390; 0, .015, .030, or .060 mg/kg) or a D2-like (sulpiride; 0, 5, 10, or 20 mg/kg) receptor antagonist, respectively. Ethanol-induced stimulation was suppressed by SCH23390 or sulpiride. The dopaminergic antagonists had no effect on blood ethanol concentration (Experiments 2a and 2b). In Experiment 3, 2.5 g/kg ethanol increased dopamine concentration in striatal tissue as well as locomotor activity in infant Wistar rats. Adding to our previous results showing a reduction in ethanol induced activity by a GABA B agonist or a nonspecific opioid antagonist, the present experiments implicate both D1-like and D2-like dopamine receptors in ethanol-induced locomotor stimulation during early development. According to these results, the same mechanisms that modulate ethanol-mediated locomotor stimulation in adult rodents seem to regulate this particular ethanol effect in the infant rat.Developmental Psychobiology 10/2009; 52(1):13-23. · 3.16 Impact Factor
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ABSTRACT: Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also the metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in the thalamus. In contrast, alcohol intoxication caused a significant increase in [1-(11)C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in the cerebellum and the smallest in the thalamus. In heavy alcohol drinkers [1-(11)C]acetate brain uptake during alcohol challenge tended to be higher than in occasional drinkers (p<0.06) and the increases in [1-(11)C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-(11)C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (i.e. ketogenic diets) may have in alcoholics undergoing alcohol detoxification.NeuroImage 08/2012; 64C:277-283. · 6.13 Impact Factor