Aldehyde dehydrogenase activity in rat cerebral structures

By means of the quantitative histochemical method aldehyde dehydrogenase (AldDG; acidic phosphatase 1.2.1.3.) activity has been studied in neuronal structures of all parts of the rat CNS. The greatest activity has been revealed in cytoplasm of receptor (nucleus of the mesencephalic tract trigeminal nerve-1,100 stipulated units) and effector (all motor nuclei of the trunk and spinal cord: 500-800 stipulated units) cerebral neurons. In perikaryons and axons of most of the intercalated neurons AldDG activity is not great (200-300 stipulated units). A positive correlation is found between distribution of AldDG activity among the forebrain structures, on the one hand, and density of dopaminergic terminals, dopamine content and MAO activity of these structures--on the other. In the metencephalon similar correlation is found between AldDG activity and noradrenaline content and density of serotoninergic terminals. A direct dependence is stated of AldDG activity on phylogenic age of the cerebral structures. The data presented demonstrate that AldDG activity is connected with those cerebral structures that are supposed to possess, in the process of common and mediatory metabolism, a high level of natural synthesis of aldehydes.     

Localization of alcohol and aldehyde dehydrogenases in the human spinal cord and brain

Location of aldehyde dehydrogenase (AldDG) and alcohol dehydrogenase (ADG) has been studied in 38 nuclei of the human brain. Neurons with a high AldDG activity predominate in the nucleus of the descending root of the trigeminal nerve, motor nuclei of the craniocerebral nerves (trigeminal, facial, abducent, blocking, sublingual, supraspinal), motor nuclei of the anterior horns of the spinal cord, lateral vestibular nucleus, posterior nucleus of the vagus nerve, pedunculopontine nucleus, superior salivary nucleus, and in the nucleus of Westphal-Edinger-Jacobovich. Neurons with a moderate AldDG activity predominate in the superior olivary complex, nucleus of the lateral loop, parabrachial (pigmented) mesencephalic nucleus and reticular lateral nucleus. A low enzymatic activity is specific for neurons of the pons proper, inferior vestibular nucleus, trapezoid body of the inferior olivary complex, dentate nucleus of the cerebellum, reticular nucleus of the tegmen of Bekhterev's pons and posterior nucleus of Gudden's suture. A high ADG activity is revealed in piriform neurons of the cerebellar cortex. Functional importance of ADG and AldDG activity in the brain is discussed.     

Acute and short term effects of ethanol on membrane enzymes in rat brain

Changes in the biophysical and biochemical character of membranes brought about by ethanol have been emphasized in the underlying mechanism of alcohol toxicity. Membrane enzymes such as Na⁺, K⁺ activated ATPase, 5-nucleotidase, and -glutamyl transpeptidase were studied in cerebral cortex, cerebellum, and brain stem of rats subjected to acute and short term ethanol toxicity. Acute ethanol toxicity was induced by intraperitoneal injection of 1 ml of 7M ethanol per 100 g body weight of rat and the animals were sacrificed half an hour after the administration. Short term ethanol toxicity was induced by intraperitoneal injections of 0.5 ml (7 M ethanol) per 100 g weight of the rat for 7 days and the animals were sacrificed half an hour after the last injection. In acute ethanol toxicity the activity of Na⁺, K⁺-activated ATPase was found to decrease significantly in cerebral cortex and brain stem, while in short term alcohol toxicity, the activity was found to increase in cerebral cortex and cerebellum. The activity of -glutamyl transpeptidase was found to increase in all the three regions in acute and short term ethanol toxicity. No change in the activity of 5-nucleotidase was observed in any of the regions either in acute or in chronic ethanol toxicity. While a significant increase in the activity of adenosine deaminase was found in cerebral cortex, cerebellum, and brain stem in acute ethanol toxicity, the same was found to decrease significantly in cerebral cortex and a persistent increase in brain stem in short term ethanol toxicity. The above changes in the activities of the enzyme were discussed with reference to the well known changes in the membrane structure and consequent alteration in brain function.This work forms part of a Ph.D. thesis.     

Experimental alcoholism in rats. Effect of acute ethanol intoxication on the in vitro incorporation of ( 3 H)leucine into neuronal and glial proteins

Abstract— Ethanol administered in vivo or in vitro during incubation of brain slices was studied with respect to its effect on brain protein synthesis. In the in vivo series the rats were given a single intraperitoneal injection of ethanol 3 h before death. Slices of cerebral cortex and liver were incubated in isotonic saline media containing [³H]leucine. Amounts of free and protein-bound radioactivity were determined. Subcellular fractions and fractions enriched in neuronal perikarya and in glial cells were prepared from cortical slices subsequent to incubation, and the specific radioactivity determined for each cell type. The incorporation of [³H]leucine into brain proteins was inhibited while incorporation into liver proteins was stimulated in ethanol-treated rats. The levels of TCA-soluble radio-activity, however, did not differ between the ethanol group and the controls. In the fractionated material from cerebral cortex, the specific radioactivity in the neuronal fraction was unaffected by ethanol, while the radioactivity in the glial fraction was significantly depressed. In vitro administration of ethanol induced a non-linear response in both brain and liver, with depression of leucine incorporation into proteins of cerebral cortex at all concentrations used. When brain slices were exposed to ethanol in vitro, in concentrations corresponding to the in vivo experiments, a similar reduction of the leucine incorporation into the glial fraction was obtained. Incorporation of leucine into subcellular fractions from whole brain cortex was also investigated. The specific sensitivity of the glial fraction to ethanol is discussed in relation to the involvement of the different cell types with transport processes in the brain.     

Possible involvement of Fyn kinase in ethanol-stimulated Cas tyrosine phosphorylation in rat cerebellum and cerebral cortex

In the present study, we have investigated the effect of intraperitoneal injection of ethanol (3.5 g/kg) on tyrosine phosphorylation in rat brain. Immunoblot analysis using an antiphosphotyrosine antibody revealed that a 130-kDa protein band was detected in the brain extract in response to ethanol administration. This ethanol-stimulated tyrosine phosphorylation of the 130-kDa protein was found in the brain but not in the heart, liver or thymus. The 130-kDa phosphotyrosine-containing protein was identified by immunoprecipitation to be Cas, a crk-associated src substrate. This ethanol-stimulated tyrosine phosphorylation of Cas was observed most prominently in the cerebellum and the cerebral cortex. We further examined the possible involvement of Fyn kinase in ethanol-stimulated Cas tyrosine phosphorylation. Immunecomplex kinase assay showed that Fyn was activated in the cerebellum and cerebral cortex of ethanol-administered rats. Immunoprecipitation experiments also showed that Fyn was co-immunoprecipitated with an anti-Cas antibody in these regions from ethanol-administered rats. Furthermore, exogenous Fyn was shown to phosphorylate Cas from cerebellum and cerebral cortex in vitro. These findings indicate that ethanol stimulates tyrosine phosphorylation of Cas in rat cerebellum and cerebral cortex, and that Fyn may be involved in the process.     

Effects of Chronic Ethanol Administration on Serotonin Metabolism in the Various Regions of the Rat Brain

Changes in serotonin (5-HT) and 5-hydroxy indole acetic acid (5-HIAA), its major metabolite, in cerebral cortex, corpus striatum and hippocampus were investigated at 10^th and 21^st days of chronic ethanol ingestion in Wistar rats. Ethanol (7.2% v/v) was given to rats in a modified liquid diet. Biochemical analysis was performed in two groups of ethanol-treated and control rats (n = 6 for each group). Rats in each group were decapitated at the 10^th and 21^st days of ethanol consumption. Brains were removed and cerebral cortex, corpus striatum and hippocampus were dissected. 5-HT and 5-HIAA levels were measured in respective brain regions by using high performance liquid chromatography. In cerebral cortex and corpus striatum, 5-HT levels were significantly lower than control at the 10^th day of ethanol consumption. At the 21^st day, the levels tended to remain low, but not significantly different statistically. In hippocampus, 5-HIAA levels were significantly higher than control at 10^th day of ethanol consumption. Increased 5-HIAA level returned to control values at the 21^st day of ethanol consumption. Our results suggest that, 5-HT clearly seems to play a critical role in the brain at the 10^th day of chronic ethanol consumption.     

Inhibition of Histamine Synthesis in Brain by α-Fluoromethylhistidine, a New Irreversible Inhibitor: In Vitro and In Vivo Studies

a-Fluoromethylhistidine (α-FMH), a new potent inhibitor of histidine decarboxylase (HD), has been used for in vitro and in vivo studies of brain HD. Following a preincubation with (+)-α-FMH, brain HD activity was inhibited in a time-dependent and concentration-dependent manner. The enzyme activity was not restored by overnight dialysis against standard buffer. The (–) antimer of α-FMH was ineffective. When injected intraperitoneally in a single dose of 20 mg/kg, (±)-α-FMH induced a complete loss in HD activity in cerebral cortex and hypothalamus as well as in peripheral tissues, such as stomach. At a dosage of 100 mg/kg (±)-α-FMH did not alter histamine-N-methyltransferase, DOPA decarboxylase, and glutamate decarboxylase activities. The maximal decrease of HD activity occurred after 2 h in both cerebral cortex and hypothalamus, but the time course of the recovery of enzyme activity was slower in the cerebral cortex. The enzyme activity reached control value within 3 days in hypothalamus and was not fully restored after 4 days in cerebral cortex. Contrasting with the diminished HD activity, a substantial concentration of histamine remained present in five regions of mouse brain. Thus, α-FMH is a highly specific irreversible inhibitor of brain HD activity and its efficacy makes it useful to study the physiological role of brain histamine.     

Acute and Long-Term Effects of Chlorpromazine on Glutamine Synthetase and Glutaminase in Rat Brain

The effect of administration of chlorpromazine on the activity of glutamine synthetase and glutaminase and the content of glutamate and gamma-aminobutyric acid (GABA) in different regions of rat brain was studied in an investigation of the possible role of these amino acids in the lowering of the seizure threshold following prolonged administration of chlorpromazine. Chlorpromazine was administered at a dose of 20 mg/kg of body weight s.c. For the acute study, the animals were killed 20 min after a single injection. For the long-term study, the animals were treated every day with the same dose for 21 days and were killed 20 min after the last injection. The results showed an increase in glutamate level in each brain region investigated following long-term administration, but only in the cerebral cortex after a single dose. GABA levels showed an increase in the brainstem only in acute experiments. Glutamine synthetase activity was increased in all three regions after a single dose and only in cerebral cortex after long-term administration. Glutaminase activity showed a decrease in cerebral cortex only after long-term administration of the drug. These results suggest the possible occurrence of a state of increased excitability in the brain as a result of long-term administration of chlorpromazine, thus contributing to the known complication of seizures.     

Differential Regulation of GABAA Receptor Gene Expression by Ethanol in the Rat Hippocampus Versus Cerebral Cortex

Abstract: Previous research has shown that chronic ethanol consumption dramatically alters GABA_A receptor α₁ and α₄ subunit gene expression in the cerebral cortex and GABA_A receptor α₁ and α₆ subunit gene expression in the cerebellum. However, it is not yet known if chronic ethanol consumption produces similar alterations in GABA_A receptor gene expression in other brain regions. One brain region of interest is the hippocampus because it has recently been shown that a subset of GABA_A receptors in the hippocampus is responsive to pharmacologically relevant concentrations of ethanol. Therefore, we directly compared the effects of chronic ethanol consumption on GABA_A receptor subunit gene expression in the hippocampus and cerebral cortex. Furthermore, we investigated whether the duration of ethanol consumption (14 or 40 days) would influence regulation of GABA_A receptor gene expression in these two brain regions. Chronic ethanol consumption produced a significant increase in the level of GABA_A receptor α₄ subunit peptide in the hippocampus following 40 days but not 14 days. The relative expression of hippocampal GABA_A receptor α₁, α₂, α₃, α_2/3, or γ₂ was not altered by either period of chronic ethanol exposure. In marked contrast, chronic ethanol consumption for 40 days significantly increased the relative expression of cerebral cortical GABA_A receptor α₄ subunits and significantly decreased the relative expression of cerebral cortical GABA_A receptor α₁ subunits. This finding is consistent with previous results following 14 days of chronic ethanol consumption. Hence, chronic ethanol consumption alters GABA_A receptor gene expression in the hippocampus but in a different manner from that in either the cerebral cortex or the cerebellum. Furthermore, these alterations are dependent on the duration of ethanol exposure.     

Brain benzodiazepine binding sites in ethanol dependent and withdrawal states

The brain benzodiazepine system has been implicated to be important in both the mechanism, and treatment of ethanol related syndromes. In this report evidence is presented which indicates that "peripheral type" benzodiazepine binding sites are probably more relevant than "central type" receptors for the neurochemical consequences of ethanol dependence and withdrawal states. Utilizing radioreceptor binding techniques 20-50% increases in the binding of [3H]RO-5-4864 (a "peripheral type" ligand) to brain membranes derived from rat cerebral cortex, cerebellum and hippocampus are observed in ethanol dependent rats. These increases persist for 3 days after cessation of ethanol. The number of [3H]RO-5-4864 binding sites in cerebellum returns to normal during 4-7 days after ethanol withdrawal. In all brain areas examined no changes were observed in the "central type" benzodiazepine receptor as judged by [3H]-ethyl-Beta-carboline-3-carboxylate, BCCE binding. Scatchard analysis revealed that the number of [3H]RO-5-4864 binding sites is increased in each brain area while the affinity was unchanged.     

Ethanol withdrawal increases glutathione adducts of 4-hydroxy-2-hexenal but not 4-hydroxyl-2-nonenal in the rat cerebral cortex

Ethanol withdrawal increases lipid peroxidation of the polyunsaturated fatty acid (PUFA) docosahexaenoate (22:6; n-3) in the CNS. To further define the role of oxidative damage of PUFAs during ethanol withdrawal, we measured the levels of glutathione adducts of 4-hydroxy-2-hexenal (GSHHE) and 4-hydroxy-2-nonenal (GSHNE) as biomarkers of brain lipid peroxidation of n-3 and n-6 PUFAs, respectively. In this study rats received an ethanol-containing diet for 6 weeks followed by withdrawal ranging from 0 to 7 days. GSHHE content was elevated (> 350%) in the cerebral cortex after 2 days of withdrawal with no change in GSHNE. The levels of GSHHE were significantly greater (2- to 20-fold) than those of GSHNE in multiple brain regions. Experiments demonstrated that intoxication and withdrawal did not alter the enzymatic rate of formation of GSHHE or GSHNE, but the rate of formation of GSHHE was higher (～ 50%) than that of GSHNE. These results indicate that selective oxidative damage to n-3 PUFAs occurs in the cerebral cortex as a result of ethanol withdrawal and that 4-hydroxy-2-hexenal is metabolized to the GSH adduct more efficiently than HNE.     

Melatonin reverses pinealectomy-induced decrease of benzodiazepine binding in rat cerebral cortex

Pinealectomy of rats resulted in significant depression of benzodiazepine receptors (assessed by [³H]flunitrazepam binding) in cerebral cortex 3–14 days after surgery without affecting their affinity significantly. A single s.c. injection of melatonin (800 μg/kg body wt) restored the depressed brain benzodiazepine receptor sites. Single melatonin injections (up to 1600 μg/kg) to intact rats did not affect brain benzodiazepine binding when injected at either morning or evening hours. Daily melatonin treatment to intact rats for 5 days augmented benzodiazepine receptor density in brain (morning injections) or its dissociation constant (evening injections). Melatonin added in vitro to rat cerebral cortex membranes only slightly depressed [³H]flunitrazepam binding at 100 μM concentrations. These results point out a link between pineal activity and benzodiazepine receptor function in rats. They also indicate that pharmacological doses of melatonin affect benzodiazepine binding sites in rat cerebral cortex.     

Effects of ammonia on monoamine oxidase and enzymes of GABA metabolism in mouse brain.

Acute and chronic ammonia toxicity was produced in the mice by intraperitoneal injection of ammonium chloride (200 mg/kg) and by exposure of mice to ammonia vapours (5% v/v) continuously for 2 days and 5 days respectively. The ammonia content was elevated in the cerebellum, cerebral cortex and brain stem and in liver. In acute ammonia intoxication there was a decrease in the monoamine oxidase (MAO) activity in all the three regions of brain. In chronic ammonia toxicity (2 days of exposure) a significant increase in the activity of MAO was observed in the cerebral cortex while in cerebellum and brain stem there was a significant decrease. In cerebral cortex and cerebellum there was a rise in the activity of MAO as a result of exposure to ammonia vapours for 5 days. A significant decrease was observed in the activity of glutamate decarboxylase (GAD) in all the three regions of the brain both in acute and chronic ammonia toxicity (2 days). There was a decrease in the activity of this enzyme only in the cerebral cortex in the animals exposed to ammonia for 5 days. The activity of GABA-aminotransferase (GABA-T) showed a significant rise in cerebellum and a fall in the brain stem in acute ammonia toxicity. In chronic ammonia toxicity GABA-T showed a rise in all the three regions of brain. Chronic ammonia toxicity produced a significant decrease in the content of glutamate in all the three regions without a significant change in the content of aspartate. GABA and glutamine. The content of alanine increased in all the three regions of brain under these experimental conditions. The ratio of glutamate + aspartate/GABA and glutamate/glutamine showed a decrease in all the three regions as a result of ammonia toxicity.     

Effects of acute and chronic ethanol administration on thromboxane and prostacyclin levels and release in rat brain cortex

The effects of acute (3 g/kg i.p. two hours before sacrifice) and chronic (6% in drinking water and libitum for 15 days) ethanol administration to male rats (200 g body weight) on basal levels and release of TxB2 and 6-keto-PGF1 alpha in brain cortex were studied. Also the effects of chronic ethanol (30 days) on the fatty acid composition of brain cortical tissue and liver phospholipids were investigated. Acute treatment reduced basal levels of 6-keto- PGF1 alpha in brain cortical tissue (rats sacrificed by microwave radiation) and decreased the accumulation of 6-keto-PGF1 alpha in brain cortex after post-decapitation ischemia (PDI). Basal TxB2 levels were also reduced in brain cortex, but TxB2 release during PDI was enhanced. Chronic treatment (15 days) induced changes of TxB2 and 6-keto-PGF1 alpha levels and release during PDI in brain cortex less pronounced than those observed after acute treatment. The reduced effectiveness of chronic ethanol on brain vasoactive eicosanoids suggest adaptation processes. After chronic treatment (30 days), the fatty acid composition of brain cortex total phospholipids were not significantly modified. Changes of eicosanoid production after ethanol were thus independent from modifications of the fatty acid precursor pool(s). Ethanol-induced changes in the production of vascular eicosanoids in the CNS may be of relevance to the action of the compound on the CNS and may also have implications for the clinic.     

Methylmercury distribution, metabolism, and neurotoxicity in the mouse brain

Methylmercury distribution, biotransformation, and neurotoxicity in the brain of male Swiss albino mice were investigated. Mice were orally dosed with [203 Hg]methylmercury chloride (10 mg/kg) for 1 to 9 days. Methylmercury was evenly distributed among the posterior cerebral cortex, subcortex, brain stem, and cerebellum. The The anterior cerebral cortex had a significantly higher methylmercury concentration than the rest of the brain. The distribution of methylmercury's inorganic mercury metabolite was found to be uneven in the brain. The pattern of distribution was cerebellum greater than brain stem greater than subcortex greater than cerebral cortex. The order of the severity of histological damage was cerebral cortex greater than cerebellum greater than subcortex greater than brain stem. There was no correlation between methylmercury distribution in the brain and structural brain damage. However, there was a relationship between the distribution of methylmercury's inorganic mercury metabolite and structural damage in the anterior cerebral cortex (positive correlation) and the anterior subcortex (negative correlation). There was also a positive correlation between the fraction of methylmercury's metabolite of the total mercury present and structural brain damage in the anterior cerebral cortex. This study suggests that biotransformation may have a role in mediating methylmercury neurotoxicity.     

Effect of chronic emotional stress and low dose ethanol on the level of neuronal cell adhesion molecule and glial fibrillary acidic protein in rat brain

The effect of chronic emotional stress and ethanol on NCAM and GFAP levels in cerebral cortex, hippocampus, striatum, cerebellum and medulla-ponts was investigated. We report about increase of NCAM and GFAP concentrations in the cerebral cortex and decline of the total protein contents in the investigated brain areas of middle-sleep rats under the stress conditions. Ethanol in the dose of 0.5 g/kg during 7 days evoked opposite changes of NCAM and GFAP concentration and elevation of the total protein level in medulla-pons. In the other brain areas level changes of only one (any) of the two investigated neurospecific proteins were observed. Ethanol injections to the stressed rats normalized the relative weights of adrenals and the level of total protein in the brain areas but didn't normalize the behavioral activity in an "open field" test. Besides, we observed a dramatic increase of GFAP level (over 10 times) in the medulla-pons which may be connected with glioses. These results suggest the specific changes of NCAM and GFAP contents under the chronic emotional stress which don't correlate with changes in the hypophysis-adrenals system.     

Distribution of alcohol dehydrogenase mRNA in the rat central nervous system. Consequences for brain ethanol and retinoid metabolism.

The localization of alcohol dehydrogenase (ADH) in brain regions would demonstrate active ethanol metabolism in brain during alcohol consumption, which would be a new basis to explain the effects of ethanol in the central nervous system. Tissue sections from several regions of adult rat brain were examined by in situ hybridization to detect the expression of genes encoding ADH1 and ADH4, enzymes highly active with ethanol and retinol. ADH1 mRNA was found in the granular and Purkinje cell layers of cerebellum, in the pyramidal and granule cells of the hippocampal formation and in some cell types of cerebral cortex. ADH4 expression was detected in the Purkinje cells, in the pyramidal and granule cells of the hippocampal formation and in the pyramidal cells of cerebral cortex. High levels of ADH1 and ADH4 mRNAs were detected in the CNS epithelial and vascular tissues: leptomeninges, choroid plexus, ependymocytes of ventricle walls, and endothelium of brain vessels. Histochemical methods detected ADH activity in rodent cerebellar slices, while Western-blot analysis showed ADH4 protein in homogenates from several brain regions. In consequence, small but significant levels of ethanol metabolism can take place in distinct areas of the CNS following alcohol consumption, which could be related to brain damage caused by a local accumulation of acetaldehyde. Moreover, the involvement of ADH in the synthesis of retinoic acid suggests a role for the enzyme in the regulation of adult brain functions. The impairment of retinol oxidation by competitive inhibition of ADH in the presence of ethanol may be an additional origin of CNS abnormalities caused by ethanol.     

Effects of ethanol on brain monoamine content of spontaneously hypertensive rats (SHR)

Spontaneously hypertensive rats (SHR) were administered either 2.4 g/kg ethanol or an isocaloric glucose daily for 4 weeks and the levels of norepinephrine (NE), epinephrine (EP), dopamine (DA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in different brain regions were determined. Results indicated a 3-fold increase in NE level in brain stem and hypothalamus and more than 2-fold increase in DA in corpus striatum in alcohol-treated rats as compared to controls. There was a significant increase in the level of DA in the corpus striatum but the levels in cerebral cortex, brain stem and hippocampus were decreased instead. Decreases in 5-HT levels were found in hypothalamus, brain stem, cortex and cerebellum of alcohol-treated brain as compared to untreated controls. These results indicate alterations of the biogenic amine contents in different regions of the SHR brain after chronic ethanol ingestion. Since stimulated release of biogenic amines in the SHR brain has been implicated in the regulation of blood pressure, changes due to ethanol ingestion may be a risk factor in hypertensive patients.     

Decreased dopamine D2 receptor function in cerebral cortex and brain stem: their role in hepatic ALDH regulation in ethanol treated rats

Ethanol exerts numerous pharmacological effects through its interaction with various neurotransmitters. The dopaminergic pathway is associated with cognitive, endocrine, and motor functions, and reinforcement of addictive substances or behaviours. Aldehyde dehydrogenase (ALDH) is a vital enzyme involved with alcohol metabolism and detoxification. In the present study, we investigated the role of cerebral cortex and brain stem dopamine D₂ receptors in the functional regulation on ALDH enzyme activity, in ethanol administrated rats. Two groups of rats were selected viz. control and alcoholic. Cerebral cortex, brain stem and the liver dopamine content was decreased significantly (P < 0.05, 0.05, 0.001, respectively) and homovanillic acid/dopamine (HVA/DA) ratio has significantly increased (P < 0.05, 0.001 and 0.001), respectively in ethanol treated rats when compared to control. Scatchard analysis of [³H]YM-09151-2 binding to synaptic membrane preparations of cerebral cortex and brain stem showed a significant decrease (P < 0.001, 0.05, respectively) in B _max in ethanol treated rats compared to control and the K _d also decreased significantly (P < 0.05). The ALDH analysis showed a significant increase (P < 0.05) in V _max in cerebral cortex, plasma and liver of experimental rats when compared with control without having significant change in brain stem but with decreased K _m (P < 0.001). Our results suggest that decreased function of dopamine mediated through DA D₂ receptor in the cerebral cortex and brain stem enhanced the brain, plasma and liver ALDH activity in ethanol treated rats. This ALDH regulation has significance to correct alcoholics from addiction due to allergic reaction observed in aldehyde accumulation.