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Long-term ethanol self-administration with repeated ethanol deprivation episodes changes ethanol drinking pattern and increases anxiety-related behaviour during ethanol deprivation in rats.

In order to study the dynamics of ethanol drinking behaviour, male Wistar rats were given the free choice between tap water, and 5, 10 and 20% ethanol solutions. After 8 weeks of continuous access, the animals were repeatedly deprived of the ethanol solutions for 3 days every 4 weeks. In the first experiment, drinking patterns were recorded for 24 h with an electronic drinkometer device, at different time-points of ethanol experience and after an ethanol deprivation episode. The preference for more highly concentrated ethanol solutions as well as ethanol consumption increased with continuing ethanol experience. Furthermore, after the ethanol deprivation episode, the animals immediately and preferentially drank from the 20% ethanol solution, the most highly concentrated ethanol solution offered. Additionally, the number of drinking bouts, particularly at the 10 and 20% ethanol solutions, was increased during the first hour after ethanol re-presentation. In a second experiment, the effects of repeated ethanol deprivation experience, inherent in this self-administration paradigm, on anxiety-related behaviour were tested on the elevated plus-maze. Repeated ethanol deprivation proved to be more anxiogenic than the first deprivation experience. Taken together, these findings suggest that ethanol deprivation is anxiogenic in long-term voluntarily ethanol-drinking rats, which is increased by repeated ethanol deprivation experience. The possibility that anxiety during ethanol deprivation might contribute to the 'relapse'-like drinking behaviour is discussed.

Alcohol Drinking↗

[Ethanol metabolism and pathobiochemistry of organ damage--1992. II. Relation between ethanol metabolism and free radicals, and the metabolism of saccharides and amino acids. Ethanol as a carcinogen. Drug interactions with ethanol].

Ethanol metabolism induces formation of free radicals which are responsible for lipid peroxidation of biological membranes with subsequent aldehyde formation (malondialdehyde,4-hydroxy-nonenal). These aldehydes are competitive or mixed inhibitors of aldehyde dehydrogenase, and they cause an increase in hepatocellular toxicity of aldehydes. The activity of antioxidative systems in human body after chronic as well as acute ethanol intake is being reduced. Interference of ethanol metabolism and gluconeogenesis is caused by inhibition of intake substrates or by decrease NADH/NAD+, ratio in hepatocyte. The blood level of glucose decreases, lactate level increases as well as the ration of lactate, pyruvate and NADH/NAD+ which inhibit cytosole pyruvate carboxykinase. An acute ethanol administration reduces the concentration of most amino acids in plasma by ethanol oxidation impacts on increase of NADH/NAD+ ratio or by mechanism mediated by beta-adrenergic receptors. Chronic alcoholics develop tolerance to decreased plasmatic levels of amino acids. Accumulation of proteins in liver may be explained by larger amount of proteins binding to fatty acids, and also by diminished degradation of proteins with decreasing autophagosome and autolysosome formations. Alcohol is one of carcinogenic factors. Ethanol, acetaldehyde and originating free radicals impaired the DNA repairing enzyme. Binding itself to DNA, acetaldehyde changes DNA properties. Ethanol may also function as a co-carcinogen due to its ability to increase disolution and absorption of carcinogens. Chronic alcoholism induces cytochrome P450 which takes part in the activation and metabolism of carcinogens. Mutual interaction of drugs metabolism and ethanol is connected mainly with cytochrome P450-MEOS. Acute ethanol intake inhibits MEOS, as MEOS gives preference to ethanol as a substrate, however, chronic alcoholism induces MEOS.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

Effects of sweetened ethanol solutions on ethanol self-administration and blood ethanol levels.

The enhancement of voluntary self-administration of ethanol by sucrose or saccharin was tested in conjunction with measurements of blood ethanol levels. Adult male rats were given access to both tap water and one of five solutions: 0.125% saccharin, 10% sucrose, ethanol, saccharin+ethanol, or sucrose+ethanol. The rats receiving the sucrose+ethanol solution drank consistently more ethanol (>5 g/kg/day) than did the rats receiving the saccharin+ethanol solution (<3 g/kg/day) or ethanol only (<2 g/kg/day). Both sweetened solutions produced higher ethanol consumption during these periods than ethanol alone. However, no significant differences in blood ethanol levels were found between the sucrose+ethanol and saccharin+ethanol conditions, when tested at different intervals on Day 44 or Day 45 of ethanol consumption. Following 45 days of consumption, no change in the bicuculline seizure threshold was observed in the ethanol-consuming rats compared to the controls. In a separate study using 90 naive rats, rats were gavaged with ethanol (1, 2, or 3 g/kg) containing either 10% sucrose (n=10 for each dose of ethanol), 0.125% saccharin (n=10 for each dose of ethanol), or ethanol alone (n=10 for each dose of ethanol), and blood was collected from the tip of the tail 30, 60, 180, 300, and 540 min later and analyzed for ethanol concentrations. Sucrose significantly decreased the resultant blood ethanol levels at several time points following gavage. These results indicate that sucrose can significantly alter blood ethanol levels and that chronic self-administration of a sweetened ethanol solution for 6 weeks does not produce ethanol dependence.

Alcohol Drinking↗

Diurnal variation in plasma ethanol levels of TO and CBA mice on chronic ethanol drinking or ethanol liquid diet schedules.

Diurnal variation in blood and plasma ethanol levels (BACs) has been observed in animals undergoing chronic ethanol treatment, but the information available is insufficient to determine whether the different patterns seen are due to differences in ethanol administration schedules or to strain of the animal. In this study, we have compared plasma ethanol levels in males of two mouse strains with no innate preference for ethanol, TO and CBA, during two commonly employed chronic ethanol treatment schedules. Ethanol was administered in solution as sole drink (CED) (10% or 20% w/v ethanol) for 4 weeks, or in liquid diet form (ELD), (3.5% w/v ethanol for 2 days, then 7% for 5 days). Mice were housed eight per cage on a 12-h light cycle (0900-2100 hours). Plasma ethanol concentration was monitored over the 24-h period. Activity of liver alcohol dehydrogenase (ADH) was measured between 0900 and 1100 hours. CBA mice showed greater variability in body weights than TO mice, which weighed more throughout the period of study and had significantly higher total energy intakes. TO mice consumed more ELD than CBA mice. Following an initial 2-day period of 3.5% ELD, both strains decreased their diet intake when ethanol content of the diet was increased to 7% w/v, which resulted in weight loss. Mice on the CED schedules decreased their fluid intake with increasing concentration of ethanol in the drinking solution. Highest daily ethanol intakes were observed in mice on ELD (19.1 +/- 1.7 and 22.2 +/- 0.6 g/kg body weight in CBA and TO mice, respectively). Marked diurnal variation in plasma ethanol levels was observed, which was dependent on the treatment schedule, strain and method of ethanol administration. Highest levels were found in mice on the ELD schedule (104.8 +/- 7.7 mM in CBA mice, 113.5 +/- 14.5 mM in TO mice), peaking at 1900 and at 0900 hours in CBA and TO mice, respectively. Lower plasma ethanol concentrations were reached in mice on the CED schedules, peaking at midnight (34.6 +/- 8.1 mM and 35.4 +/- 8.8 mM in CBA and TO mice on 20% CED, respectively, and 3.7 +/- 1.2 mM and 6.6 +/- 2.1 mM in CBA and TO mice on 10% CED). Naive CBA mice had slightly higher liver ADH activity as compared to their TO counterparts. No effect of 10% CED on liver ADH activity was found in either mouse strain. In conclusion, we have confirmed the importance of monitoring plasma ethanol levels during chronic treatment, as there is marked diurnal variation, dependent on the light/dark cycle. Factors such as strain of the animal and the method of delivery of ethanol are also important, whereas liver ADH plays a minor role. Monitoring the daily ethanol consumption is insufficient to predict the resulting plasma levels of the drug.

Alcohol Dehydrogenase↗

Effect of chronic ethanol treatment and selective breeding for sensitivity to ethanol on calcium release induced by inositol trisphosphate or ethanol from brain and liver microsomes.

Our previous work showed that ethanol increases the resting intracellular free calcium concentration (CAi) in synaptosomes and releases calcium from an inositol trisphosphate (IP3)-insensitive calcium store of brain microsomes. In this report, we investigated the effects of chronic ethanol treatment and selective breeding for hypnotic sensitivity to ethanol on IP3 and ethanol-stimulated calcium release from brain and liver microsomes. Chronic ethanol treatment did not alter IP3-stimulated calcium release from brain microsomes or ethanol-stimulated calcium release from brain or liver microsomes. Chronic ethanol treatment increased the spontaneous release of calcium from brain but not liver microsomes. In microsomes isolated from cerebellum or cerebral cortex of long-sleep (LS) and short-sleep (SS) mice, ethanol and IP3 released calcium in a concentration dependent manner. The amount of calcium released by ethanol and IP3 was larger in microsomes isolated from cerebellum than microsomes from cerebral cortex. However, the amount of calcium released by ethanol and IP3 did not differ between the two lines in either brain area. These results do not support the idea that the hypnotic effects of ethanol are due to ethanol-induced calcium release from a nonmitochondrial intracellular calcium store in brain tissue. The development of ethanol tolerance and dependence also does not appear to be associated with altered ability of ethanol to release calcium from non-mitochondrial intracellular stores; however, effects of chronic ethanol exposure on spontaneous release of intracellular calcium could alter neuronal function in ethanol dependence.

Alcohol Drinking↗

Short and prolonged periods of maternal separation and voluntary ethanol intake in male and female ethanol-preferring AA and ethanol-avoiding ANA rats.

BACKGROUND: Genetic as well as environmental factors can affect the propensity for psychopathology and/or drug dependence. Maternal separation represents an animal experimental model that is useful in studies of effects of early life experiences. The authors have established a protocol for short and prolonged periods of maternal separation to study adult neurochemistry, behavior, and ethanol intake and have previously reported alterations in ethanol intake in Wistar rats and ethanol-preferring rats. The aim of the current study was to more thoroughly study how early life experiences affect an inherited propensity for high and low ethanol intake, respectively, in male and female ethanol-preferring AA (Alko alcohol) and ethanol-avoiding ANA (Alko, Non-Alcohol) rats. METHODS: AA and ANA pups were assigned to one of three different rearing conditions: 15 min (MS15) or 360 min (MS360) of daily maternal separation in litters or normal animal facility rearing (AFR) during postnatal days 1 to 21. In adulthood, voluntary ethanol intake was investigated using the two-bottle free choice paradigm. RESULTS: In male ethanol-preferring AA rats, MS15 resulted in a lower intake and fewer high-preferring animals at 8% and 10% ethanol compared with MS360 rats. The male MS360 rats had a higher ethanol intake at 8% and 10% ethanol in comparison with AFR rats. In contrast, the female AA MS15 and MS360 rats had a lower ethanol intake and a lower preference for the 10% ethanol solution compared with the female AA AFR rats. In male and female ANA rats, no major separation-induced effects were found. CONCLUSIONS: The current results show that genetic inheritance can be affected by environmental manipulations in AA rats with an inherent high ethanol intake. The findings in female ethanol-preferring AA rats give further evidence of a differential outcome of maternal separation in male and female rats, as previously shown.

Alcohol Drinking↗

The effects of high ethanol doses on rates of ethanol oxidation in rats. A reassessment of factors controlling rates of ethanol oxidation in vivo.

1. Ethanol was oxidised more slowly by rats which were given an ethanol dose of 5.1 g/kg than by rats which were given an ethanol dose of 1.4 g/kg. 2. A positive correlation was found between [lactate]/[pyruvate] ratios and rates of ethanol oxidation. 3. Acetaldehyde concentrations varied widely between rats, but in some cases were high enough to influence rates of ethanol oxidation. 4. Liver alcohol dehydrogenase levels were just sufficient to account for ethanol oxidation rates observed in vivo. 5. Pre-administration of a large ethanol dose (6.5 g/kg) did not alter mean [lactate]/[pyruvate] ratios or ethanol oxidation rates during metabolism of test doses of 2.5 g/kg. 6. Injection of pyruvate did not increase rates of ethanol oxidation. 7. The results do not support suggestions that a high-Km ethanol oxidising system plays an important role in vivo, that increased rates of ethanol oxidation can be induced by large, acute ethanol doses or that the rate of NADH reoxidation controls rates of ethanol metabolism. 8. The results support other evidence which has indicated that the level of alcohol dehydrogenase is the major factor limiting rates of ethanol oxidation in vivo.

Acetaldehyde↗

[Ultrasound-guided renal cyst puncture and 95% ethanol injection. Part 1: Estimation of ethanol levels in the blood and urine following 95% ethanol injection].

Seventeen solitary renal cysts were punctured with the ultrasound-guided procedure and 26-91% of the cyst volume was replaced with 95% ethanol used as a sclerosing agent of the cyst wall. Ethanol was injected through a 7 F pigtail ureteral catheter, allowed to remain in place for 20 minutes and removed through the catheter. Recovery rate of ethanol was 82.4%. The maximum blood level of ethanol was obtained 30 to 60 minutes after injection, while the maximum urinary excretion rate was observed after 60 to 120 minutes. The maximum blood levels of ethanol ranged from 0.015 to 0.339 mg/ml. There was a positive correlation between injected volume of ethanol and the maximum blood level (r = 0.66) or the total amount of urinary excretion during 12 hours (r = 0.72). Residual ethanol concentrations in the body were calculated from injected volume and recovery rate of ethanol. Only 2.3% of the residual ethanol in the body was excreted in the urine during the first 12 hours after injection. However, urine/blood ratio of ethanol 1 hour after injection was tremendously high with a wide variation between 1.6 and 230.5. Therefore, a large part of the ethanol absorbed from the cyst wall seems to be excreted directly from the kidney, not entering general circulation. From the estimation of the blood and urine levels of ethanol, it is concluded that 95% ethanol can be applied to the renal cyst wall as a sclerosing agent through the percutaneous ultrasound-guided procedure in the case of good recovery of ethanol.

Adult↗

Ethanol-stress interaction: immediate versus delayed effects of ethanol and handling on stress responses of ethanol-consuming rats.

Rats screened for voluntary ethanol intake (high, medium, and low ethanol-preferring rats and non-ethanol-exposed controls) were given acute immobilization stress either immediately following the ethanol screening procedure, or after a 20 day period without access to ethanol. Among animals examined for stress responses immediately after ethanol screening, it was observed that water-only control rats developed significantly less frequent and less severe gastric stress ulcers than rats in all ethanol-exposed groups. This result suggests that ethanol, stress and routine handling may have contributed to ulcer formation in these animals. In contrast, among rats tested for stress responses after 20 days without ethanol, it was observed that the high ethanol-preferring animals showed less severe stress ulcers. These results indicate that among high ethanol-consuming animals, the presence of ethanol enhances ulcer severity, while prior experience with ethanol consumption does not appear to predispose rats to exacerbated stress gastric pathology.

Alcohol Drinking↗

Ethanol-ecstasy (MDMA) interactions in rats: preserved attenuation of hyperthermia and potentiation of hyperactivity by ethanol despite prior ethanol treatment.

Recreational use of ecstasy, or (+/-)-3,4-methylenedioxymethamphetamine (MDMA), is often associated with other drugs, among which ethanol is one of the most common. Little is known, however, about the interaction between these two drugs. Using a daily ethanol and/or MDMA administration regimen, we recently showed that ethanol potentiated the hyperactivity (in the home cage), but attenuated the hyperthermia induced by MDMA. The prevention of hyperthermia occurred only on the first of four daily ethanol-MDMA treatments, indicating possible tolerance to ethanol. In order to test the tolerance hypothesis, we treated Long-Evans adult male rats with ethanol on 4 consecutive days prior to their first treatment with MDMA-ethanol. Our results first confirmed that ethanol (1.5 g/kg, i.p.) potentiates the psychomotor effects of MDMA (10 mg/kg, i.p.), while attenuating its pyretic effects (6.6 mg/kg, i.p.). The results also showed that both the potentiation of locomotor activity and the attenuation of hyperthermia by ethanol are not at all altered by prior ethanol treatment. This indicates that tolerance to ethanol per se does not account for what appears to be tolerance to the ethanol-MDMA combination, thus indicating that ethanol-MDMA combination likely has unique pharmacological effects.

Animals↗

Increased alcohol dehydrogenase independent ethanol oxidation at high ethanol concentrations in isolated rat hepatocytes: the effect of chronic ethanol feeding.

Rates of ethanol oxidation in isolated rat hepatocytes increased with increasing ethanol concentrations even at near-saturation of the alcohol dehydrogenase (ADH) pathway. After inhibition of ADH by pyrazole, approximately 30% of ethanol-oxidizing activity remained and this activity of the non-ADH pathway was also dependent upon ethanol concentration. The apparent Km of th non-ADH pathway for ethanol was 13 mM, which is comparable to the value for the microsomal ethanol oxidizing system. Inhibition of catalase by azide affected the activity of the non-ADH pathway by less than 10%. After chronic ethanol feeding, the rates of ethanol oxidation in isolated hepatocytes and liver slices increased significantly compared to those in pair-fed controls. This adaptive increase of ethanol oxidation was more striking at a high ethanol level (30 mM) than at a low one (10 mM). Significant differences between the two groups remained even after inhibition of ADH and catalase. The results suggest that the microsomal ethanol oxidizing system may account for the major part of the non-ADH pathway.

Alcohol Oxidoreductases↗

Genetic correlational analyses of ethanol reward and aversion phenotypes in short-term selected mouse lines bred for ethanol drinking or ethanol-induced conditioned taste aversion.

Short-term selective breeding created mouse lines divergent for ethanol drinking (high drinking short-term selected line [STDRHI], low drinking [STDRLO]) or ethanol-induced conditioned taste aversion (CTA; high [HTA], low [LTA]). Compared with STDRLO, STDRHI mice consumed more saccharin and less quinine, exhibited greater ethanol-induced conditioned place preference (CPP), and showed reduced ethanol stimulation and sensitization under some conditions; a line difference in ethanol-induced CTA was not consistently found. Compared with LTA, HTA mice consumed less ethanol but were similar in saccharin consumption, sensitivity to ethanol-induced CPP, and ethanol-induced locomotor stimulation and sensitization. These data suggest that ethanol drinking is genetically associated with several reward-and aversion-related traits. The interpretation of ethanol-induced CTA as more genetically distinct must be tempered by the inability to test the CTA lines beyond Selection Generation 2.

Alcohol Drinking↗

Intestinal lymph formation and fat absorption: stimulation by acute ethanol administration and inhibition by chronic ethanol administration and inhibition by chronic ethanol feeding.

The acute administration of ethanol, either in lipid emulsions administered intraduodenally or in liquid diets given by gastric tube, increased the flow of intestinal lymph and the output of proteins and dietary lipids into the lymph, mainly in the 1st hr after administration. During this time, the intraduodenal administration of ethanol (0.75 g per kg of body weight), without exogenous lipids, increased the flow of lymph without changing the lymph lipid output. Stimulation of the lymph flow with neostigmine or by increasing the fluid load also enhanced the output of lymph proteins and the transport of exogenous lipids from the intestinal lumen into the lymph. To study the chronic effects of ethanol, rats were pair-fed liquid diets containing either ethanol (36% of calories) or isocaloric carbohydrate for 3 to 4 weeks. Thereafter, the lymph changes were measured after administration of equal lipid loads with and without ethanol. The administration of an acute ethanol dose to rats chronically fed alcohol moderately increased the lymph flow, but did not change the output of dietary lipids. Furthermore, rats chronically fed alcohol responded to a dietary challenge devoid of ethanol with increases in both lymph flow and dietary lipid output which were not as great as those of pair-fed controls. Thus, acute ethanol administration has a marked stimulatory effect both on the formation of intestinal lymph and on the transport of deitary fat. By contrast, chronic ethanol feeding inhibits these acute effects of ethanol, and, in addition, appears to have moderate inhibitory effect on lipid absorption.

Acute Disease↗

[Effect of long-term ethanol administration (2). Free type and bound type ethanol and related substances contents of the urine from ethanol administrated rats, indices in the serum, and renal tissues].

Histological effects of ethanol on the kidney were published in our previous report. In the present paper, results of the following measurement will be reported: contents of ethanol and related substances in the urine, both free and bound types, collected during the periods from 30 minutes to 11 hours after ethanol administration to rats, and ACE, alpha-GST, LPO, 25(OH)-D3, 1 alpha-25(OH)2-D3, 24, 25(OH)2-D3 in the serum of rats which had ethanol every day for a month. These will be reported together with histological observation of the kidney excised immediately after the blood sample was collected. The measurement of free and bound types ethanol, acetaldehyde, acetone and methanol in the urine was made up to 11 hours after administration of 4 g/kg b.w./day, p.o. and its results showed the highest contents at 9 hours after the administration. Bound type acetic acid showed the high contents at both 90 minutes and 9 hours after the administration. In 11 hours free type ethanol and acetaldehyde recovered their pre-administration value but as to the bound type only acetic acid recovered it. In the serum of the rats which were ethanol 4 g/kg b.w./day, oral administrated for a mouth, ACE showed significantly high value and 1 alpha, 25(OH)2-D3 and 24, 25(OH)2-D3 showed significantly low value relative to the control. Also alpha-GST showed a low value. In the kidney of the same rats the following changes were observed: swelling of glomerulus, thickening of basement membrane of glomerulus, PAS positive deposits in glomerulus, proliferation of mesangial cell, proliferation of juxtaglomenular cell, dilation of tubular lumen, swelling of tubular epithelial cell, its falling, hyaline droplet in tubular epithelial cell, cell infiltration to interstitial tissue, and basophilic tubule. There was not only difference between findings in the control and those in the liver and the brain of the rats which showed changes above-mentioned. As described above, changes were seen in the renal tissue caused by ethanol administration and in this connection changes in indices related to renal function were observed, too. Furthermore, urinary ethanol and related substances, not only free type but also bound type, that went through the kidney were observed for a long period time. The bound type, in particular, was observed for longer duration and hence effects of ethanol on the kidney were surely assumed. Presently longer term experiments are proceeding and other indices connected with renal functions are being studied.

Administration, Oral↗

Novel uncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist MRZ 2/579 suppresses ethanol intake in long-term ethanol-experienced rats and generalizes to ethanol cue in drug discrimination procedure.

Previous findings suggested that drugs modulating glutamatergic neurotransmission could be useful in the treatment of alcohol dependence. This study examined the effects of chronic and acute treatment with MRZ 2/579 (1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride), a novel uncompetitive N-methyl-D-aspartate receptor antagonist, on voluntary ethanol intake in long-term ethanol-experienced rats. Rats were implanted with mini-osmotic pumps delivering either 9.6 mg/day MRZ 2/579 or vehicle, and the effects of treatment on the alcohol deprivation effect (ADE) were studied in a four-bottle home cage-drinking paradigm. The same rats were tested for a second ADE 3 weeks later in the absence of the drug. In a second experiment long-term ethanol-experienced rats trained in an operant free-choice ethanol self-administration paradigm with concurrent water received acute MRZ 2/579 treatment (0-4 mg/kg i.p.) before a 23-h session either during basal drinking or during the ADE. In an additional experiment, MRZ 2/579 (0.5-4 mg/kg i.p.) was tested for generalization to the ethanol cue in a drug discrimination procedure. Chronic MRZ 2/579 treatment selectively abolished the increased ethanol intake during the ADE. This effect depended on the presence of the drug. Acute MRZ 2/579 treatment (2 and 4 mg/kg) had a short-lasting reductive effect on lever pressing for ethanol, but not for water, both during the ADE and basal drinking. MRZ 2/579 dose dependently generalized to the ethanol cue in the drug discrimination experiment. It is concluded that MRZ 2/579 might exert its reducing effect on ethanol intake by substituting for some of the stimulus properties of ethanol.

Alcohol Drinking↗

Inhibition of NMDA-evoked electrophysiological activity by ethanol in selected brain regions: evidence for ethanol-sensitive and ethanol-insensitive NMDA-evoked responses.

Our laboratory has previously shown that systemically administered ethanol inhibits NMDA-evoked electrophysiological activity in some, but not all, neurons in the medial septum. In the present report, it was found that ethanol, when applied locally via electro-osmosis, potently inhibited NMDA-evoked neuronal activity in a current-dependent manner in the inferior colliculus and hippocampus. In contrast, locally applied ethanol failed to inhibit NMDA-evoked activity in the lateral septum. The inhibition by ethanol of NMDA-evoked activity in the inferior colliculus was specific, in that ethanol failed to inhibit neuronal activity of the inferior colliculus evoked by the excitatory neurotransmitter glutamate. These findings indicate that ethanol can specifically inhibit NMDA-evoked activity in vivo via a local action, and that the ability of ethanol to inhibit NMDA-evoked activity varies regionally in brain. The possibility that these results are explained by the existence of two types of NMDA receptors, one sensitive to ethanol, the other insensitive to ethanol, is discussed.

Animals↗

Ethanol-Metrecal diets: I. effects of different levels of ethanol-derived kilocalories on consumption of diet, body weight and grams of ethanol ingested.

Three experiments investigated the relationship between ethanol consumption and the percentage of ethanol-derived kilocalories contained in liquid diets. Rats were chronically maintained on diets where different concentrations of ethanol (10%, 12%, 14%) were added to Metrecal so that 41%, 49% and 57% of all kilocalories consumed were derived from ethanol. The ethanol-Metrecal diet served as the sole source of calories. Results demonstrated that rats can be maintained for extended time periods on diets where ethanol contributed approximately 50% of the daily kilocalories. Inspection of consummatory profiles revealed that an initial decrease occurred in volume of diet consumed when levels of ethanol were increased. This was followed by a gradual increase in the level of consumption until a new asymptotic level was established. Grams of ethanol/kg of body weight remained relatively constant over the range of ethanol concentrations employed. The results were discussed in respect to three factors controlling consummatory behavior--sensory stimuli, caloric intake and quantity of ethanol ingested.

Acoustic Stimulation↗

Cerebral membranes isolated from rats consuming ethanol or gestationally exposed to ethanol have increased susceptibility to modulation by ethanol.

The actions of ethanol on membrane fluidity were examined. All assays were carried out using fluorescence techniques in the P2 fraction of crude synaptosomes isolated from rat brain. Subchronic treatment of rats with ethanol revealed a significant increase in order at the membrane interior. In vitro addition of ethanol to P2 fractions prepared from treated rats revealed a significant rise in fluidity at the membrane core that was not found in corresponding P2 fractions from untreated rats. The withdrawal of ethanol from subchronically treated rats revealed no significant alterations in membrane fluidity. However, in vitro addition of ethanol to P2 fractions prepared from these animals produced an increase in fluidity at the membrane centre. This effect was not observed in corresponding control rats. Rat pups that were gestationally exposed to ethanol also failed to show any significant differences in membrane fluidity compared with control rats. However, in vitro addition of a challenge dose of ethanol to P2 fractions resulted in a significant rise in fluidity not found in pups from untreated mothers. These findings suggest that the process of adaptation to chronic ethanol may be dissected into two separable events: one frequently reported effect that alters membrane fluidity and one that modulates membrane susceptibility to ethanol-induced perturbations.

Alcoholism↗