Multiphasic Consequences of the Acute Administration of Ethanol on Cerebral Glucose Metabolism in the Rat

Wake Forest University School of Medicine, Department of Physiology and Pharmacology, Medical Center Boulevard, Winston-Salem, NC 27157, USA
Pharmacology Biochemistry and Behavior (Impact Factor: 2.78). 11/1998; 61(2):201-206. DOI: 10.1016/S0091-3057(98)00089-6


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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    • "Ethanol significantly increased dopamine concentration in striatum, a result that is consistent with previous research with adult rats showing that relatively high ethanol doses induce an increment in local cerebral rates of glucose metabolism in striatum (Lyons et al., 1998) and elevation of dopamine levels in this area (Melendez et al., 2003). We acknowledge that increases in dopamine content may not reflect dopamine release directly. "
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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.
    Full-text · Article · Jan 2009 · Developmental Psychobiology
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    • "Dopamine depletions (Reynolds et al., 1998) or a combined treatment with MAO inhibitors (Maragos et al., 1999) attenuated 3-NPA striatal effects. Interestingly, as has been demonstrated, ethanol treatment clearly affects the striatum as well (Lyons et al., 1998). Thus, it is possible that DA-dependent ROS generation in the striatum were the mechanism for the interaction between 3-NPA and ethanol. "
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    ABSTRACT: The antioxidant enzyme catalase by reacting with H(2)O(2), forms the compound known as compound I (catalase-H(2)O(2)). This compound is able to oxidise ethanol to acetaldehyde in the CNS. It has been demonstrated that 3-nitropropionic acid (3-NPA) induces the activity of the brain catalase-H(2)O(2) system. In this study, we tested the effect of 3-NPA on both the brain catalase-H(2)O(2) system and on the acute locomotor effect of ethanol. To find the optimal interval for the 3-NPA-ethanol interaction mice were treated with 3-NPA 0, 45, 90 and 135min before an ethanol injection (2.4mg/kg). In a second study, 3-NPA (0, 15, 30 or 45mg/kg) was administered SC to animals 90min before saline or several doses of ethanol (1.6 or 2.4g/kg), and the open-field behaviour was registered. The specificity of the effect of 3-NPA (45mg/kg) was evaluated on caffeine (10mg/kg IP) and cocaine (4mg/kg)-induced locomotion. The prevention of 3-NPA effects on both ethanol-induced locomotion and brain catalase activity by L-carnitine, a potent antioxidant, was also studied. Nitropropionic acid boosted ethanol-induced locomotion and brain catalase activity after 90min. The effect of 3-NPA was prevented by l-carnitine administration. These results indicate that 3-NPA enhanced ethanol-induced locomotion by increasing the activity of the brain catalase system.
    Full-text · Article · Jan 2007 · Neuropharmacology
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    • "These discrepancies are therefore likely to reflect, in part, differences in response to alcohol between strains. Other variables known to influence the effects of alcohol on brain glucose metabolism such as the timing of measurements after alcohol (Lyons et al., 1998), past alcohol history of the animals (Porrino et al., 1998), whether alcohol is self-administered versus given by the investigator (Williams-Hemby et al., 1996) and dose and route of administration (Williams-Hemby and Porrino, 1997) are also likely to contribute to some of the discrepancies. In humans, imaging studies have shown that alcohol-induced changes in brain glucose metabolism are also sensitive to prior histories of chronic alcohol use (Volkow et al., 1990) and to gender (Wang et al., 2003). "
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    ABSTRACT: Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.
    Full-text · Article · Feb 2006 · NeuroImage
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