Brain Aldehyde Dehydrogenase Activity Research Articles

Alterations in brain aldehyde dehydrogenase activity modify ethanol-induced conditioned taste aversion.

The role of peripherally and centrally acting acetaldehyde in ethanol-induced conditioned taste aversion (CTA) was investigated using various enzyme manipulations. Cyanamide, an aldehyde dehydrogenase inhibitor (ALDH) elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4MP), an alcohol dehydrogenase inhibitor, prevents peripheral accumulation of acetaldehyde by cyanamide. Under both treatment conditions brain and liver ALDH activity is inhibited. Water-deprived rats were pretreated 4 hr prior to fluid presentation with intraperitoneal injections of saline (S+S), 4-methylpyrazole (4MP+S), cyanamide (S+C), or 4-methylpyrazole + cyanamide (4MP+C). Subsequently, animals were presented with a novel saccharin solution followed immediately by intraperitoneal injection of one of three doses of ethanol (0.4, 0.8, or 1.2 g/kg) or saline vehicle on four occasions. Results suggested that animals pretreated with cyanamide (groups S+C and 4MP+C) drank significantly less saccharin after conditioning with a subthreshold dose of ethanol (0.4 g/kg) in comparison to groups S+S and 4MP+S. Moreover, at the conditioning dose of 1.2 g/kg, cyanamide-treated animals demonstrated an attenuation of CTA compared to the other two groups. These effects cannot be attributed to elevated blood acetaldehyde levels since pretreatment with 4MP+C prevented peripheral acetaldehyde accumulation. A characteristic common to both cyanamide-treated groups was the inhibition of brain ALDH. It is therefore suggested that brain ALDH may play a role in the mediation of ethanol-induced CTAs. It is conceivable that ALDH plays this role by regulating the levels of acetaldehyde in brain.

Assay of brain aldehyde dehydrogenase activity using high-performance liquid chromatography with electrochemical detection

A method has been developed for assay of aldehyde dehydrogenase (ALDH) in brain tissue or in other tissues containing low ALDH-activity. The aldehyde of dopamine was used as the substrate, and the 3,4-dihydroxyphenylacetic acid formed was measured using high-performance liquid chromatography (HPLC) with electrochemical detection. The aldehyde was prepared enzymatically by incubating dopamine with a monoamine-oxidase preparation from rat liver mitochondria in the presence of Na +-bisulfite in 10 m m K +-phosphate buffer (pH 7.5). Rat brain homogenates were incubated in 50 m m Na +-pyrophosphate buffer (pH 8.8) containing 0.5 m m NAD + and 5 μ m aldehyde. The reaction was terminated with perchloric acid containing Na +-bisulfite to trap excess of the aldehyde. The acid supernatants were injected on a reverse-phase HPLC column and elution was performed with citrate buffer, pH 2.50. The method permits assay with 1–10 mg of brain tissue with an overall precision of 3%. The assay rate was 5–6 samples per hour.

P-72 - Alcohol preference and brain aldehyde dehydrogenase activity in mice

P-72 - Alcohol preference and brain aldehyde dehydrogenase activity in mice

Subcellular and perisynaptic distribution of rat brain aldehyde dehydrogenase activity.

The nuclear mitochondrial and synaptosomal fractions of rat brain were each found to contain some 25-30% of the total aldehyde dehydrogenase activity. The cytoplasmic fraction had a very low total aldehyde dehydrogenase activity. There were differences in the distribution of the activity when different aldehydes were used as substrates, suggesting the presence of isoenzymes in the various subcellular compartments. When rats were treated intracisternally with 6-hydroxydopamine there was no change in brain aldehyde dehydrogenase activity, although the noradrenaline content and the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were markedly decreased. Treatment with 6-hydroxydopamine also had no significant effect on the aldehyde dehydrogenase activity in retinal homogenates. The results suggest that the aldehyde dehydrogenase activity in rat brain is predominantly outside the catecholaminergic nerve terminals.

Suppression of alcohol drinking with brain aldehyde dehydrogenase inhibition

Calcium cyanamide, an aldehyde dehydrogenase (ALDH) inhibitor used in the treatment of alcoholism, strongly suppressed voluntary ethanol drinking by rats. Such inhibitors have generally been believed to act primarily by limiting drinking through acetaldehyde accumulation after ethanol consumption. Administration of a low dose of 4-methylpyrazole (4-MP) that abolished acetaldehyde accumulation did not, however, remove the suppression produced by cyanamide. 4-MP alone did not affect the unsuppressed alcohol intake by Long Evans rats or the drinking by rats of the ANA strain developed for low levels of ethanol consumption. When given from the start with cyanamide, 4-MP did affect the development of the suppression, but probably by its effect in lessening the degree of brain ALDH inhibition: a high correlation (r= +0.825, p<0.001) was found between brain ALDH activity and ethanol consumption. The results suggest that cyanamide suppresses alcohol drinking also in the absence of acetaldehyde accumulation probably by some action related to its direct inhibition of brain ALDH.

Brain aldehyde dehydrogenase activity in rat strains with high and low ethanol preferences

The activity of aldehyde dehydrogenase in subcellular fractions of whole brain homogenates from the AA and ANA rat strains developed respectively for high and low ethanol preferences has been studied. No significant strain or sex differences between naive AA and ANA rats were found. In ethanol-experienced rats some strain and sex differences were found, the most consistent being higher enzyme activity in AA females than in males both with aliphatic and aromatic aldehyde substrates. However, contrary to previous findings no relation between brain aldehyde dehydrogenase activity and drinking behavior was found in the AA and ANA rat strains.

Aldehyde dehydrogenase inhibitors and voluntary ethanol drinking by rats.

Aldehyde dehydrogenase (ALDH) inhibitors, cyanamide (200 mg or 40 mg/kg food) and coprine (N5-(hydroxycyclopropyl)-L-glutamine, 500 mg/kg food), strongly suppressed, with similar time courses, the free-choice consumption of 10% v/v ethanol. The suppression occurred with both continual and alternate access to alcohol. The presence of the inhibitors (plus 4-methylpyrazole to prevent acetaldehyde accumulation) did not affect ethanol-induced (1.5 g/kg i.p.) motor impairment on the tilting plane, but the rats on alternate-day access, which consumed more alcohol on days of access, were significantly less impaired.

Brain aldehyde dehydrogenase: Adaptive increase following prolonged ethanol administration in rats

Chronic ethanol ingestion (8–12 g/kg bodyweight per day) by rats led to a significant rise in the levels of total brain aldehyde dehydrogenase (ALDH) activity. This effect was noted after 60 days from the start of the ethanol regimen and was found to parallel reduction in levels of liver ALDH activity. Neither the normal levels of whole brain ALDH activity nor ALDH inducibility were significantly affected by age. Furthermore, while the normal level of brain ALDH was consistently higher in females, the magnitude of induction of the enzyme was larger in males. Finally, there were differences in normal levels of ALDH as well as in ALDH inducibility between the cortex, the midbraindiencephalon and the cerebellum. The data suggest that induction of brain ALDH activity may reflect a physiological mechanism that mediates the adaptation of neurones in the brain to some of the acetaldehyde-mediated effects of ethanol. The implications of these findings to the development of tolerance to ethanol are discussed.

Electrical stimulation and lesions of the medial forebrain bundle of the rat: Changes in voluntary ethanol consumption and brain aldehyde dehydrogenase activity

Repeated sessions of electrical stimulation or lesions in the ventral aspect of the medial forebrain bundle (VMFB) region of the brain in rats resulted in a significant increase and a decrease in voluntary ethanol (10% v/v) intake, respectively. Whole brain and midbrain-diencephalon (MB-DE) aldehyde dehydrogenase (ALDH) were measured in different groups of experimental and control animals before, immediately after, and 30 days after the termination of the stimulation regimen, or 8 days and 30 days after the induction of the lesions. By the end of the stimulation regimen, the levels of MB-DE ALDH of the experimental (ethanol-drinking: stimulated) animals were significantly higher than those of control animals (ethanol-drinking: nonstimulated, water-drinking: stimulated, and water-drinking: nonstimulated). A marked decrease in MB-DE ALDH activity was noted in lesioned animals but not in cyanamide-treated or in implanted control animals. Neither the stimulation nor the lesions had any demonstrable effect on whole brain ALDH activity. Cyanamide administration caused a pronounced decrease in ethanol intake and in levels of liver ALDH activity. The increase in MB-DE ALDH activity in the ethanol-drinking, stimulated animals was attributed to the interaction between the VMFB activation and the ethanol drinking, while the reduction in ALDH activity was attributed to the degeneration of biogenic-amine-containing nerve fibers.

Brain and liver aldehyde dehydrogenase activity and voluntary ethanol consumption by rats: relations to strain, sex, and age.

Voluntary ethanol consumption and brain and liver aldehyde dehydrogenase (ALDH) activity were measured in male and female rats of the Tryon Maze-Bright (S1), Tryon Maze-Dull (S3), and Wistar strains. The levels of brain ALDH measured in the different groups, corresponded well to the levels of ethanol consumption, while differences in liver ALDH corresponded well to only the strain differences in ethanol intake. Within individual groups, levels of ethanol consumption correlated better with levels of brain and liver aldehyde-oxidizing capacity. Age affected both voluntary ethanol intake and liver ALDH levels, but there were no systematic relations between the two effects. Age did not significantly affect the cerebral-aldehyde oxidizing capacity. It is argued that inherent variation in brain ALDH activity may be a principal biochemical counterpart of the differences in ethanol intake amoung different strains and sexes of laboratory rats.

Brain and liver aldehyde dehydrogenase: Relations to ethanol consumption in wistar rats

Activity of brain and liver aldehyde dehydrogenase (ALDH) was measured in male Wistar rats given free access to ethanol and water for 50 days. Brain ALDH activity was better correlated with levels of absolute ethanol intake than liver ALDH, but the magnitude of the relations between enzyme activity and ethanol consumption varied depending on whether animals were regulating their ethanol consumption across different ethanol concentrations: brain and liver ALDH were better correlated with ethanol intake in regulating animals. By contrast, brain ALDH was relatively more important than liver ALDH in predicting ethanol consumption in non-regulating animals. The results suggest that brain and liver ALDH may mediate ethanol consumption in rats by regulating some aspects of the dose-effect relations between acetaldehyde and ethanol.