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: Neurobiological studies have identified brain areas and related molecular mechanisms involved in alcohol abuse and dependence. Specific cell types in these brain areas and their role in alcohol-related behaviors, however, have not yet been identified. This study examined the involvement of cholinergic cells in inbred alcohol-preferring rats following 1 month of alcohol drinking. Cyclin-dependent kinase 5 (Cdk5) immunoreactivity (IR), a marker of neuronal plasticity, was examined in cholinergic neurons of the nucleus accumbens (NuAcc) and prefrontal cortex (PFC) and other brain areas implicated in alcohol drinking, using dual immunocytochemical (ICC) procedures. Single Cdk5 IR was also examined in several brain areas implicated in alcohol drinking. The experimental group self-administered alcohol using a 2-bottle-choice test paradigm with unlimited access to 10% (v/v) alcohol and water for 23 h/d for 1 month. An average of 6 g/kg alcohol was consumed daily. Control animals received identical treatment, except that both bottles contained water. Rats were perfused and brain sections were processed for ICC procedures. Alcohol drinking resulted in a 51% increase in Cdk5 IR cholinergic interneurons in the shell NuAcc, while in the PFC there was a 51% decrease in the percent of Cdk5 IR cholinergic interneurons in the infralimbic region and a 46% decrease in Cdk5 IR cholinergic interneurons in the prelimbic region. Additionally, single Cdk5 IR revealed a 42% increase in the central nucleus of the amygdala (CNA). This study identified Cdk5 neuroadaptation in cholinergic interneurons of the NuAcc and PFC and in other neurons of the CNA following 1 month of alcohol drinking. These findings contribute to our understanding of the cellular and molecular basis of alcohol drinking and toward the development of improved region and cell-specific pharmacotherapeutic and behavioral treatment programs for alcohol abuse and alcoholism.Alcoholism Clinical and Experimental Research 09/2006; 30(8):1322-35. · 3.42 Impact Factor
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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. · 2.60 Impact Factor
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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.Neuropharmacology 01/2007; 51(7-8):1137-45. · 4.11 Impact Factor