Effect Of Chronic Ethanol Ingestion Research Articles

Effects of chronic ethanol ingestion on long-term potentiation remain even after a prolonged recovery from ethanol exposure.

Previous work in our laboratory has demonstrated that memory formation, a behavioral process thought to be at least in part attributed to hippocampal functioning, is severely attenuated following 5 months of chronic ethanol treatment (CET) and 2 months of recovery from CET. Additionally, 48 h following CET, a well-recognized physiological correlate of memory formation, long-term potentiation (LTP), is reduced in the hippocampus. We hypothesized that the reduction in LTP may in part contribute to the behavioral deficit in memory formation, which is a permanent consequence of CET. In order for the reduction of LTP to be involved with the permanent deficit in memory acquisition, it too must be present following a prolonged period of ethanol abstinence. The present study examined the permanent effect of CET on LTP. Animals were fed a nutritionally complete, ethanol containing diet for 28 weeks and then allowed a 5-7 month abstinence period. A control group was fed the same diet except sucrose was isocalorically substituted for ethanol. Neurophysiological methods measured the capacity of synaptic connections onto CA1 pyramidal cells to support LTP in response to a variety of conditioning trains. The magnitude of LTP was reduced in CET animals as compared with pair-fed controls. LTP induction is mediated by activation of the N-methyl-d-aspartate (NMDA) receptor complex and is modulated by activation of gamma-aminobutyric acid (GABA)ergic synaptic transmission. The effect of CET on LTP magnitude may be due to effects on the NMDA-induced induction itself or on the GABAergic modulation of induction.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol-induced changes in membrane ATPases: inhibition by iron chelation

The effect of chronic ethanol intake, with and without an iron chelator, on the activity of rat membrane ATPases was investigated. Using the intragastric feeding model, male Wistar rats (250 g) were fed a liquid diet and ethanol for 1 month. In control pair-fed animals, ethanol was isocalorically replaced by dextrose. In addition to the above groups, two groups of animals (dextrose or ethanol-fed) also received an oral iron chelator (1,2-dimethyl-3-hydroxypyrid-4-one, L 1) (25 mg/kg/day for 30 days). The blood ethanol levels were maintained between 150 and 300 mg/dL. Red cells were washed immediately with ice-cold saline, membranes were prepared, and ATPases were measured. The mean Ca 24+ pump ATPase in animals fed ethanol was lower than in dextrose-fed controls. In contrast, Na +/K + pump ATPase was enhanced following chronic ethanol treatment. The addition of 1 1) to the diet prevented the changes in both the Ca 2+-ATPase and Na +/K +-ATPase in ethanol-fed rats. Although the exact mechanism for the prevention of changes in ATPase activity by L 1 is unknown, it is not a result of non-specific interaction between the chelator and membranes. Incubation of purified membranes with different concentrations of L 1 for 60 min at 37° had no effect on the activity of the ATPase. In conclusion, chronic intake of ethanol specifically inhibited Ca 2+ pump ATPase and enhanced Na +/K +-ATPase in rat red blood cell membranes. The iron chelator, L 1, corrected both of these ethanol-induced changes.

Chronic ethanol ingestion modifies the renin-aldosterone axis independent of alterations in the regulation of atrial natriuretic peptide.

Using an animal model, we have investigated the effects of chronic ethanol ingestion on the regulation of atrial natriuretic peptide (ANP) synthesis and release. Male Sprague-Dawley rats were maintained for 6 weeks on a liquid diet of ethanol (up to 20% v/v) as part of a 2% solution of calf milk replacer. Weight-matched controls received an equal volume of ethanol-free solution, and normal animals drank ad libitum. All animals received rat chow throughout the experiment. This model produced physiologically relevant levels of blood ethanol, as concentrations at the time of sacrifice were 171.98 +/- 39.26 mg/dl. Plasma renin activity was significantly elevated in response to ethanol treatment, whereas circulating aldosterone concentration was reduced. No alterations in the plasma or atrial tissue levels of ANP were evident, although we did observe a significant increase in the ventricular tissue levels of ANP from 45.1 to 71.8 ng/g as a consequence of ethanol treatment. Levels of both atrial and ventricular ANP mRNA were not different between alcohol-treated and liquid-restricted control animals, although both groups showed significant increases in the amount of transcript in comparison with rats drinking ad libitum. No significant increases in either arterial blood pressure or heart/body weight ratio were observed for ethanol-treated rats. These results suggest that modifications in the renin-aldosterone axis can occur independently of alterations in the regulation of ANP under the influence of chronic ethanol ingestion.

Effects of chronic ethanol intake at a low dose on the rat brain dopaminergic system

The effects of 8-week ethanol treatment (3% v/v in drinking water) on the rat brain dopaminergic system were investigated. Chronic ethanol consumption induced a significant increase in the number of dopamine D 1 receptor sites in the caudate putamen. Conversely, no significant changes were observed in D 2 receptor density or affinity. Biochemical results were in agreement with behavioral data, as amphetamine-induced locomotor hyperactivity was significantly higher in ethanol-treated rats in comparison to controls. Moreover, grooming behavior in response to SKF 38393, a selective agonist of D 1 receptors was potentiated in ethanol-treated rats, whereas locomotor hyperactivity induced by LY 171555 (a selective agonist of D 2 receptors) was not affected by ethanol treatment. The results indicate that changes in dopamine receptors may occur in the central nervous system at levels of ethanol intake that do not induce tolerance or dependence.

The effect of chronic ethanol intake on brain NGF level and on NGF-target tissues of adult mice

The effect of ethanol consumption on the forebrain and hypothalamus of adult mice was investigated. A consistent decrease of biological activity and of nerve growth factor (NGF) immunoreactivity was observed in the hippocampus and hypothalamus of alcohol-treated mice. Biochemical studies also indicate that chronic ethanol intake causes a reduction in the level of cholineacetyltransferase in the septum, hippocampus and striatum, but not in the cortex and other brain regions. This study provides evidence that long-term ethanol intake causes impairment of brain NGF level and of the cholinergic enzyme, regulated by NGF, suggesting that NGF synthesis and/or biological activity is affected in alcohol-related brain neuropathology.

Effects of chronic ethanol ingestion on tissue elimination‐phase kinetics of procainamide in rats

AbstractThe effects of chronic ethanol ingestion on the pharmaco‐kinetics of procainamide in various tissues were studied. Ethanol‐treated rats received ethanol at 4 g/kg/day for an initial 7 days and then at 8 g/kg/day for the subsequent 21 days; control rats received isocaloric sucrose. After a single intravenous dose, the semilogarithmic procainmide concentration‐time profiles observed in hearts and kidneys of both groups of rats were similar to the previously reported biexponential profiles of procainamide concentration in blood. This finding indicates a rapid distribution equilibrium of drug in both blood and these highly perfused tissues. The profiles of drug concentration in thigh muscle and fat of both groups of rats exhibited a drug‐uptake phase during the initial 25‐min period followed by a monoexponential decline in drug concentration. For all tissues, the slopes (β values) of the curves of the drug concentration versus time were calculated on the basis of elimination‐phase data, except for fat of control rats where the predominant elimination phase was not discernible. The β values in hearts and thigh muscles of ethanol‐treated rats were significantly higher than those in the corresponding tissues of control rats. These results are evaluated in light of previously reported effects of the same ethanol treatment on the distribution pharmacokinetics and the steady‐state partition coefficients of the drug in these tissues. Possible mechanisms are proposed to account for these effects on the basis of the known diverse effects of chronic ethanol ingestion on the cellular compositions of individual organs and tissues.

Alcohol and heat tolerance in warm-acclimated rats

The effect of chronic ethanol intake and warm acclimation on the heat tolerance of rats under the influence of alcohol was studied. The animals were divided into two groups: Group 1 received water as their fluid intake and, group 2 received a 10% ethanol solution, and both groups were exposed to a temperature of 30°C for 4 weeks. Excretion of urinary catecholamines was measured prior to warm exposure at 22°C and once a week during warm exposure at 30°C. After warm acclimation a dose of alcohol 2 g/kg was injected in the rats intraperitoneally (i.p.), and then they were exposed to a heat stress of 40°C for 45 min. During warm acclimation, the controls consumed more fluid and they excreted more norepinephrine into the urine than the alcohol-fed animals during the first week. After the period of acclimation there were no significant differences in urinary excretion of catecholamines between the groups. Colonic temperature of the controls was 0.7°C higher than in the alcohol-fed animals. Acute alcohol administration (2 g/kg) increased the colonic temperature of the alcohol-fed animals during a heat stress of 40°C more than in the controls. After heat stress, the concentration of catecholamines in the blood was significantly higher in the controls. The results show that the hyperthermic effect of ethanol was more considerable in the rats whose drinking water during warm acclimation was an ethanol solution.

Effect of chronic ethanol ingestion on phosphate content of neurofilament proteins and neurofilament associated protein phosphatase in rat spinal cord

Rats were trained to drink alcohol solution by gradually increasing the ethanol content [2.5-15% (v/v)] in drinking water. After 11 months of alcohol (15% v/v) ingestion, animals were guillotined and the spinal cords were used for the preparation of neurofilaments (NF). NF triplet proteins were separated by SDS-PAGE and the phosphate contents of individual components were estimated. Results indicated a significant increase in phosphate content of 200 KD protein in alcohol fed rats (30.19 +/- 4.12 mol of phosphate/mole of protein: p less than 0.001) compared to control group (18.42 +/- 3.91 mol of phosphate/mole of protein). No significant change in the phosphate content of 150KD and 68KD components of NF were seen in experimental group. Further, the studies on NF associated protein phosphatase activity indicated a significant decrease in phosphatase activity among the alcohol fed rats (14.10 +/- 2.5 mU; p less than 0.001) against NF rich fraction as a substrate, as compared to control (20.15 +/- 2.15 mU). While the observed decrease in NF associated protein phosphatase would possibly explain the increase in phosphate content of NF proteins in alcohol fed rats, the precise mechanism of decrease in enzyme activity remains to be elucidated. Nevertheless, the change seen in phosphate content and NF associated protein phosphatase activity as a result of ethanol ingestion would possibly form the biochemical basis of some of the neuropathological changes seen in alcoholics.

Microdialysis of extracellular noradrenaline in the hippocampus of the rat after long-term alcohol intake

Intracerebral microdialysis combined with high-performance liquid chromatography and electrochemical detection was used to study the effect of chronic ethanol intake on the release of noradrenaline in the hippocampus of the awake, freely moving rat. The hippocampal sites were perfused with an artificial cerebrospinal fluid for 30 min at a rate of 2 μl/min before ethanol intake and after one and 3 months of ethanol intake. The animals received a 10% ethanol solution as their drinking fluid. The basal release of noradrenaline before ethanol drinking varied from no measurable value to 28 pg in 50 μl perfusate, possibly being dependent on the behavioral state of the animal. After one month of drinking the release had increased in 4 rats, was lower than before in two animals and remained unchanged in 3 rats. After 3 months of ethanol intake the release had increased in 7 rats out of the 9 and had remained unchanged in two. The mean amount of noradrenaline in 50 μ1 perfusate after 3 months of drinking was 52 pg. Five rats out of 9 increased their ethanol consumption during the last two months. The results suggest that chronic ethanol intake affects the release of noradrenaline in the hippocampus, but that the effect is probably dependent on the duration of intake.

Effect of Chronic Ethanol Ingestion on Lipid‐Lipid and Protein‐Lipid Interactions in Membranes:

Effect of Chronic Ethanol Ingestion on Lipid‐Lipid and Protein‐Lipid Interactions in Membranes:

Effects of Chronic Ethanol Ingestion on Pharmacokinetics of Procainamide in Rats

Blood level studies were carried out in rats to determine the effects of chronic ethanol ingestion on the distribution pharmacokinetic parameters and tissue steady-state partition coefficients of procainamide. The ethanol-treated rats received 4g/kg of ethanol daily for 28 days in Treatment A and 4 g/kg of ethanol for an initial 7 days, followed by 8 g/kg of ethanol for the subsequent 21 days in Treatment B; the control rats received isocaloric sucrose in the respective groups. As determined from two-compartment analysis of the blood level data, both ethanol treatments significantly decreased the distribution clearance (C/-d; k,2Vdc) and the apparent first-order rate constant for drug transfer from the central compartment to the tissue compartment (k12) of procainamide without affecting the total body clearance of drug (CL) or the apparent volumes of distribution of drug in the body at steady state (Vdss) and at pseudo-equilibrium (Vdp). Additionally, the apparent volume of distribution of the drug in the central compartment (Vdc) was 57-62% greater due to both ethanol treatments. Furthermore, the steady-state partition coefficients of the drug were found to be significantly lower in heart and kidneys and greater in fat of the ethanol-treated rats (Treatment B) as compared with those in the control rats. Possible mechanisms are proposed to account for these various effects in light of the known effects of chronic ethanol ingestion on the chemical composition of cell membranes of tissues and organs.

Maintenance of structural and functional characteristics of skeletal-muscle mitochondria and sarcoplasmic-reticular membranes after chronic ethanol treatment

The effect of long-term ethanol intake on the structural and functional characteristics of rat skeletal-muscle mitochondria and sarcoplasmic reticulum was investigated. Functionally, skeletal-muscle mitochondria were characterized by a high respiratory control index and ADP/O ratio and a high State-3 respiration rate with different substrates. These parameters were not significantly different in preparations from control and ethanol-fed rats, except for a small increase in the rate of oxidation of alpha-oxoglutarate/malate in the latter. In submitochondrial particles from the two groups of animals there was no significant difference in cytochrome content, ATPase activity or the activity of respiratory-chain complexes. Mitochondrial membranes from untreated and ethanol-fed rats showed no difference in the baseline e.s.r. order parameter, and both preparations were equally sensitive to disordering by ethanol in vitro. Similarly, sarcoplasmic-reticulum preparations were not significantly affected by long-term ethanol feeding with respect to Ca2(+)-ATPase activity or in baseline order parameter and susceptibility to membrane disordering by ethanol in vitro. These membranes were also equally sensitive to degradation by exogenous phospholipase A2. Ethanol feeding did not alter the class composition of mitochondrial or sarcoplasmic-reticulum membrane phospholipids, nor the acyl composition of individual phospholipid classes. Specifically, the changes in acyl composition that characteristically occur in liver microsomal phosphatidylinositol and liver mitochondrial cardiolipin were not observed in the corresponding phospholipids from skeletal-muscle membranes. In experiments where membrane preparations from liver and skeletal muscle from the same ethanol-fed animals were compared, the liver membranes developed membrane tolerance, with the muscle membranes retaining normal sensitivity to disordering effects by ethanol. It is concluded that: (a) different tissues from the same animals differ in their susceptibility to ethanol; (b) the tissue-specific lack of development of membrane tolerance correlates with a lack of chemical changes in the phospholipids and with a retention of normal function of mitochondria and sarcoplasmic reticulum; (c) effects of chronic ethanol intake on muscle function are not due to a defect in the mitochondrial energy supply.

The influence of chronic ethanol ingestion on the absorption of vitamin a by adult male rats

To determine the effect of chronic ethanol ingestion on the absorption of vitamin A, adult male rats were given 10% ethanol in drinking water for one week, 20% for the next two weeks and 30% for the last three weeks plus rat chow ad libitum. Pair-fed controls received the same amount of rat chow as that consumed by the ethanol group, but the ethanol was substituted isocalorically with starch. Ad libitum controls received rat chow only. After six weeks on these diets the animals were given 750 μg of vitamin A by stomach tube and blood was obtained from the tail at 0, 1, 2, and 3 hours after administration of the vitamin. There were no significant differences in plasma vitamin A levels among the three animal groups at time 0 (Alcohol, 17.6 μg/100 ml; pair-fed, 25.8; control, 28.3). At 1 hour, the maximum mean plasma vitamin A rise was significantly lower in the alcohol group, (47.5 μg/100 ml) than in either the pair-fed (105.5) or the control group (105.6). The findings were similar at the 2 hour interval. At 3 hours the vitamin A levels declined substantially and were no longer significantly different among the three groups. The hepatic vitamin A levels were significantly lower in the alcohol group than in the ad libitum controls. Compared to the pair-fed controls, the liver vitamin A levels were not significantly lower in the alcohol group. These findings indicate that chronic alcohol consumption by rats reduces the rate of vitamin A absorption from a test dose administered intragastrically but does not significantly alter liver vitamin A stores when compared with pair-fed controls.

Brain and Plasma Tetrahydroisoquinolines in Rats: Effects of Chronic Ethanol Intake and Diet

Brain concentrations of salsolinol (SAL), a simple tetrahydroisoquinoline (sTIQ) condensation product of dopamine (DA) and acetaldehyde, are reported to increase in chow-fed rats drinking ethanol/H2O ad libitum. However, our analyses showed that rat chow contains traces of SAL and, as previously reported, appreciable 3,4-dihydroxyphenylalanine (DOPA), a sTIQ precursor. To examine the effect of consumption of ethanol in a DOPA- and SAL-free diet on endogenous sTIQs, we analyzed two brain regions and blood plasma of rats undergoing prolonged intake (3 weeks and 23 weeks) of liquid diet containing 6.6% ethanol or isocaloric carbohydrate. SAL and three other DA-related sTIQs were quantitated using capillary gas chromatography/mass spectrometry in the selected ion mode with deuterated standards. In accord with studies on ethanol/chow-fed rats, sTIQ concentrations in hypothalamus were elevated after 3 weeks of ethanol, although after 23 weeks, hypothalamic sTIQs were either unchanged or reduced (O-methylated SAL). Furthermore, sTIQ concentrations in corpus striatum and, with one exception, plasma were not altered by ethanol ingestion for either duration. (However, 23 weeks of ethanol intake significantly reduced the striatal concentrations of DA and its acid metabolite, presumably reflecting neurotoxicity.) Reasoning that DOPA in diet might underlie the reported ethanol-dependent increases in striatal sTIQs, we found that L-DOPA supplementation (500 micrograms/rat/day) of EtOH/liquid diet-fed rats for 13 weeks tended to increase striatal SAL. Overall, the data indicate that elevations in endogenous sTIQ concentrations due to prolonged ethanol intake depend on the brain region, duration of intake, and even associated dietary constituents. In that regard, the higher striatal SAL concentrations in rats drinking ethanol ad libitum could have been facilitated by DOPA and perhaps SAL consumed in lab chow.

Hypothalamic vasopressin mRNA levels in mice are decreased after chronic ethanol ingestion

Vasopressin mRNA levels in the supraoptic and paraventricular nuclei of the hypothalamus, measured by in situ hybridization with a 35S-labeled RNA probe, were decreased by nearly 50% in C57BL/6NCR mice that had ingested an ethanol-containing diet for 7 days, and were tolerant to and physically dependent on ethanol. At 24 h after withdrawal, vasopressin mRNA levels in the supraoptic nucleus were still decreased, while levels in the paraventricular nucleus returned toward control values. Although plasma osmolality was increased in ethanol-fed mice, there was no increase in plasma vasopressin levels, possibly as a result of the effect of chronic ethanol ingestion to decrease vasopressin synthesis. In contrast, in mice that were dehydrated, but not fed ethanol, plasma osmolality, plasma vasopressin levels, and hypothalamic vasopressin mRNA all increased, as expected. The data suggest that chronic ethanol ingestion interferes with the synthesis and secretion of vasopressin, and may result in the reduced ability of an individual to respond to physiological stimuli for vasopressin secretion.

Effects of chronic ethanol intake on aromatization of androgens and concentration of estrogen and androgen receptors in rat liver

The present study was carried out to investigate if ethanol alters aromatization of androgens and concentrations of hepatic estrogen and androgen receptors. Hepatic aromatization of androgen to estrogen was significantly increased by ethanol administration. There was a significant increase in serum estrogen level but a decreased circulating testosterone level in alcohol-fed rats. Furthermore, the concentration of estrogen receptors in liver cytosol was significantly higher in alcohol-fed rats (37 ± 5.3 fmol/mg protein), as compared to the intact control value (21 ± 4.8 fmol/mg protein). However, hepatic androgen receptor levels were much lower (4.4 ± 0.5) in alcohol-fed rats than those (10.2 ± 1.4 fmol/mg protein) in control animals. Similarly, castration increased hepatic aromatization of androgens and concentrations of serum estrogen and hepatic estrogen receptors, but it decreased contents of circulating androgen and hepatic androgen receptors. These findings indicate that alcohol administration is considered a chemical form of castration, altering the hepatic steroid metabolism and sex hormone receptor contents and contributing to the pathogenesis of ferminization. A combination of alcohol-feeding and castration has no synergistic effect on the hepatic steroid receptors and aromatization, but this combination does have a more profound effect in lowering the concentration of circulating androgen.

Are the effects of chronic ethanol administration on erythrocyte membrane mediated by changes in plasma lipids?

The effect of chronic ethanol consumption on plasma and erythrocyte membrane lipids were studied in rats fed a liquid diet containing ethanol for 4 weeks and intubated with the same diet 90 min prior to killing. Control animals underwent the same treatment, except that their liquid diet did not contain ethanol, but an isocaloric amount of carbohydrates. Plasma total cholesterol, free (unesterified) cholesterol and HDL cholesterol were higher in ethanol-fed animals than in controls. Phospholipids were also higher in the plasma of ethanol-fed animals when compared to controls so that the plasma cholesterol/phospholipid ratio ( Ch PL ratio ) of the two groups did not differ significantly, regardless of the cholesterol fraction considered. Experimental and control animals did not differ either in the Ch PL ratio of their erythrocyte membranes. In view of the fact that it has been suggested that the factor determining the direction of the cholesterol exchanges between plasma and erythrocyte membranes is the equilibrium between their respective Ch PL ratios , these results are interpreted as being compatible with the hypothesis that the effect of chronic ethanol intake on erythrocyte membrane lipids is mediated through changes in plasma lipids.

The Role of Arginine Vasopressin in Alcohol Tolerance

Administration of the neuropeptide, arginine vasopressin, to animals that have acquired functional tolerance to ethanol will maintain such tolerance, even in the absence of further ethanol ingestion by the animals. In mice, this action of the peptide is mediated by central nervous system V1 receptors and requires intact brain noradrenergic systems. Autoradiographic studies have shown that some V1 receptors are localized presynaptically on catecholaminergic neuronal terminals in the mouse lateral septum, suggesting that vasopressin may act via modulation of catecholamine release. In addition, vasopressin has been found to increase mRNA levels for the proto-oncogene, c-fos, in septum and hippocampus, possibly by an action at postsynaptic receptors. Expression of c-fos, which has been hypothesized to play a role in central nervous system neuroadaptation, could transform short-term actions of vasopressin into long-term effects on ethanol tolerance. Studies with vasopressin antagonists indicate that the endogenous peptide influences tolerance, and therefore the effect of chronic ethanol ingestion on vasopressin synthesis and release was studied. In mice and rats, hypothalamic vasopressin mRNA is decreased by chronic ethanol exposure, although effects on plasma vasopressin levels differ in the two species. The effect of ethanol on extrahypothalamic vasopressin synthesis in brain is under investigation. The results suggest mechanisms by which vasopressin can produce long-term changes in central nervous system function, and provide evidence for a disturbance of vasopressin regulation during chronic ethanol ingestion.

β-Adrenergic receptor binding in brain of alcoholics

The binding of agonists and antagonists to β-adrenergic receptors in brain tissue obtained postmortem in nonalcoholic controls and matched intoxicated and sober alcoholics was measured to assess the state of the receptors and their coupling to adenylate cyclase. Binding of antagonist, iodocyanopindolol, to cerebral cortical and cerebellar membrane preparations was not different in alcoholics compared to that in controls, suggesting that the number of β-adrenergic receptors was not affected by chronic ethanol ingestion. Agonist binding data, however, indicated the loss of the high-affinity agonist binding state of the β-adrenergic receptor, representing the receptor-guanine nucleotide binding protein (G s) complex. Such changes were observed in cerebral cortex but not in cerebellum of intoxicated alcoholics. These data suggest that cerebral cortical β-adrenergic receptors are uncoupled from adenylate cyclase in these subjects. In cerebral cortical and cerebellar membranes of sober alcoholics both the high- and low-affinity agonist binding sites were observed. These findings are similar to those seen in animal studies and suggest that the effect of chronic ethanol ingestion on β-adrenergic receptor-adenylate cyclase coupling is brain region specific and reversible with abstinence. Ethanol-induced changes in the coupling of receptors to adenylate cyclase may contribute to the physiological and behavioral manifestations of alcohol abuse.

The effect of chronic ethanol ingestion on synthesis and degradation of soluble, contractile and stromal protein fractions of skeletal muscles from immature and mature rats.

1. An investigation was carried out into the response of soluble, myofibrillar and stromal protein fractions of skeletal muscle to chronic ethanol feeding. Groups of male Wistar rats, of approx. 85 or 280 g body wt., were pair-fed on a nutritionally complete liquid diet containing glucose or a diet in which 36% of the total energy was provided by ethanol. After 6 weeks, rates of protein synthesis were measured with a flooding dose of L-[4-3H]phenylalanine. 2. The protein contents of soluble, myofibrillar and stromal fractions in gastrocnemius muscle from small and large rats were decreased by ethanol feeding. Greater changes were observed in small than in large rats. 3. Fractional synthesis rates of soluble, myofibrillar and stromal proteins of gastrocnemius were all decreased by ethanol treatment. All fractions responded similarly, though percentage decreases in large rats were greater than in small rats. Absolute synthesis rates in gastrocnemius muscles were also decreased after ethanol treatment. All protein fractions responded similarly, and the magnitudes of the responses in large and small rats were also similar. 4. Fractional rates of breakdown, measured by the difference between fractional growth and synthesis rates, were apparently decreased, in both sets of rats, in all protein fractions. 5. It was concluded that chronic ethanol exposure causes perturbations in soluble, myofibrillar and stromal protein accretion by a mechanism involving unidirectional changes in protein synthesis and possibly breakdown.