Effects of alprazolam on the free-choice ethanol consumption induced by isolation stress in aged rats.

Late-onset drinking is a common problem in elderly people related to stress induced by social isolation. Experiments were performed in order to evaluate the effects of alprazolam, a benzodiazepine agonist anxiolytic, on the free-choice ethanol consumption in aged rats subjected to isolation stress. The animals we offered a two-bottle choice consumption (one of 0.2% saccharin and the other with 10% ethanol/0.2% saccharin) and then exposed to 4 days of isolation stress on an irregular, unpredictable schedule. Stress resulted in significant increase in ethanol consumption. Treatment with alprazolam (1 mg/Kg) partially reversed this adverse effect of stress.     

The effect of long-term, voluntary ethanol consumption on hepatic regeneration in rats

Previous studies have reported conflicting results regarding the effect of ethanol on hepatic regeneration. The purpose of the present study was to determine whether long-term, voluntary consumption of ethanol, within the range reported in humans, has an effect on hepatic regenerative activity in rats following partial hepatectomy. Ninety-four adult male Sprague-Dawley rats (n = 3-9/group) were studied. Based on the amount of 9% ethanol consumed over a 50-day period, low ethanol intake (0.1-1.9 g.kg-1.d-1) and high ethanol intake (2.0-4.0 g.kg-1.d-1) groups were identified. Control groups consisted of rats provided with propylene glycol in equivalent caloric amounts to the ethanol consumed by high ethanol intake rats (isocaloric group) and rats served water only (ad libitum group). An additional two groups from which ethanol was removed 5 days prior to surgery were also studied (low ethanol grace and high ethanol grace). Hepatic regeneration was determined by restitution of liver weight, [3H]thymidine incorporation into DNA, and [14C]leucine incorporation into protein 24, 48, and 72 h following partial (70%) hepatectomy. The results of the study revealed no significant differences in the rate of hepatic regeneration between low and high ethanol consuming rats or between either of these groups and isocaloric or ad-libitum fed control groups. Regeneration in low ethanol grace and high ethanol grace groups were also similar to each other and controls. Moreover, there was no correlation between mean ethanol consumption per rat and restitution of liver weight, [3H]thymidine incorporation into DNA, or [14C]leucine incorporation into protein by the regenerating liver (r = 0.0716, -0.1637, and 0.1395, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of the animals' emotional state on ethanol consumption under free-choice conditions

Voluntary ethanol consumption (20% solution) in mice of C57BL/6J strain with different experience in social agonistic confrontations was studied. It has been shown, that aggressive males daily winning other individuals did not change the level of ethanol consumption, while the submissive mice with daily experience of defeat in intermale encounters dramatically increased that level. Ethanol enhanced the behavioural reactivity of submissive animals to other individuals. It was supposed that emotionally positive or negative states differentiate the ethanol motivations in mice.     

Stress-induced consumption of ethanol by rats

Rats were maintained in a continuous choice situation for consumption of either 0.1% aqueous saccharin or 10% ethanol- 0.1% saccharin with daily tube position reversal and 24 hour fluid consumption measurement. After a stabilized baseline was achieved, groups were exposed to either no stress, or to an unpredictable schedule of isolation or immobilization stress for 14 days. During baseline and stress-exposure periods, the rats consumed predominantly the saccharin solution. Upon cessation of the stress exposures the isolation and immobilization groups markedly increased their consumption of the ethanol solution, reaching intakes as high as 9.1 g/kg/24 hours in 2-3 weeks. In addition, after 3 weeks of ethanol consumption, placement of saccharin in both tubes resulted in the stressed animals preferentially consuming from the tube that should have contained ethanol. The results suggest that unpredictable exposure to stressful stimuli can, upon cessation of exposure, induce an alcohol consummatory behavior in rats.     

Stress-induced consumption of ethanol by rats

The natural aversion of rats to ethanol was overcome by subjecting rats to immobilization stress for a two-week period during which increasing concentrations of ethanol were offered in the drinking water. The rats subjected to this regimen consumed 47% of total calories as ethanol, indefinitely, following removal of the stress. Ethanol was consumed at a rate of 17.1 g/kg body weight along with sufficient stock diet to assure adequate nutrition in the absence of ethanol.     

Growth and liver morphology after long-term ethanol consumption of rats

Ethanol was administered to female and male Wistar rats by mixing it with their drinking water. Ethanol concentrations were gradually increased up to either 8% or 15%. Female rats receiving 8% ethanol in their drinking water consumed 5-13 g, males 4-10 g daily. The ethanol/total food caloric intake percentages were 13 to 20% and 9 to 15% for female and male rats, respectively. There was no difference in body weight and relative liver weight between treated rats and their controls. Female and male rats receiving 15% of ethanol in their drinking water consumed 8-14 g ethanol per kg body weight per day. The percentages of ethanol/total food caloric intake were stabilized at about 25% for both sexes. Growth of the rats differed only slightly from controls; a tendency for a higher increase of body weight of the control rats was found. No difference in relative liver weight between ethanol-treated and control rats was observed. Microscopic examinations revealed that the ethanol treatment resulted in fat accumulation in the liver cells. A proliferation of the Smooth Endoplasmic Reticulum (SER) was more marked in the 15% dosed rats than in the 8% dosed rats and more distinct in female rats than in male rats in both dosage groups.     

Effect of compounds with anxiolytic properties on voluntary ethanol consumption by rats

The effect of different chemical anxiolytic agents on ethanol consumption has been studied on the model of experimental alcoholism in rats. The decrease of ethanol consumption was dose-dependent. The existence of non-benzodiazepine anxiolytic systems is suggested.     

The effect of Hoe-427 (an ACTH4-9 analog) on free-choice ethanol consumption in male and female rats.

Ethanol consummatory patterns of individual male and female rats and the effects of Hoe-427 (Ebiratide), an ACTH4-9 analog, thereon, were studied in a test system using 24 hour, two-bottle free choice consumption between 0.2% saccharin and 10% ethanol in 0.2% saccharin. Single, daily i.p. doses (0.03mg/rat) of either ACTH4-10 or its analog resulted in a significant reduction of daily ethanol consumption with no effects on saccharin consumption. After 4 days of treatment, male rats consistently exhibited a rebound increase in ethanol consumption; this effect was not seen in females. The daily ethanol consummatory patterns of the female animals seemed to exhibit a 4-6 day cyclic rhythymicity, suggesting an interaction with estrous cycles. These results support a role for ACTH4-10 in the initiation of ethanol consummatory behavior in rats and suggests the existence of sex differences in this phenomenon.     

Sex-dependent differences in the regulation of myocardial protein synthesis following long-term ethanol consumption

Chronic heavy alcohol consumption alters cardiac structure and function. Controversies remain as to whether hearts from females respond to the chronic ethanol intake in a manner analogous to males. In particular, sex differences in the myocardial response to chronic alcohol consumption remain unresolved at the molecular level. The purpose of the present set of experiments was to determine whether alterations in cardiac structure and protein metabolism show sexual dimorphism following chronic alcohol consumption for 26 wk. In control animals, hearts from female rats showed lowered heart weights and had thinner ventricular walls compared with males. The smaller heart size was associated with a lower protein content that occurred in part from a reduced rate of protein synthesis. Chronic alcohol consumption in males, but not in females, caused a thinning of the ventricular wall and intraventricular septum, as assessed by echocardiography, correlating with the loss of heart mass. The alterations in cardiac size occurred, in part, through a lowering of the protein content secondary to a diminished rate of protein synthesis. The decreased rate of protein synthesis appeared related to a reduced assembly of active eukaryotic initiation factor (eIF)4G.eIF4E complex secondary to both a diminished phosphorylation of eIF4G and increased formation of inactive 4Ebinding protein (4EBP1).eIF4E complex. The latter effects occurred as a result of decreased phosphorylation of 4EBP1. None of these ethanol-induced alterations in hearts from males were observed in hearts from females. These data suggest that chronic alcohol-induced impairments in myocardial protein synthesis results, in part, from marked decreases in eIF4E.eIF4G complex formation in males. The failure of female rats consuming ethanol to show structural changes appears related to the inability of ethanol to affect the regulation protein synthesis to the same extent as their male counterparts.     

Effect of an antiserum to brain gamma gamma-enolase (protein 14-3-2) on ethanol consumption by rats

The influence of intracisternal administration of antiserum to the neurospecific brain gamma gamma-enolase (aS-gamma gamma) on the consumption of 7.5% ethanol solution by rats was studied. Injection of aS-gamma gamma decreased the ethanol intake by the rats which had been drinking 15% solution of ethanol for 7 months as a single source of liquid. In vitro aS-gamma gamma caused 4-fold inhibition of the gamma gamma-enolase activity while it did not influence the alpha alpha-enolase activity. Intracisternal administration of aS-gamma gamma shifted enolase isoenzyme spectra in the direction of the decrease of gamma gamma-enolase content. It is suggested that the effect of aS-gamma gamma on ethanol consumption is due to inhibition of the activity of gamma gamma-enolase which participates in energy metabolism in neurons.     

Suppression of voluntary ethanol consumption in rats by gamma-butyrolactone

The effect of gamma-butyrolactone (GBL) on voluntary ethanol intake was studied in a group of Wistar rats in which a stable preference had been induced by exposure to increasing ethanol concentrations. These rats drank 60% of their daily fluid intake as 15% ethanol solution, corresponding to about 6 g ethanol/kg/day. GBL, injected intraperitoneally at the dose of 200 mg/kg, twice daily for 3 consecutive days, decreased ethanol intake by about 80% on the days of treatment, but did not reduce total fluid intake. Ethanol intake remained significantly reduced up to the 5th day following cessation of GBL administration. GBL, up to a concentration of 10(-3) M, inhibited neither alcohol-dehydrogenase nor aldehyde-dehydrogenase in rat liver homogenates, nor dopamine-beta-hydroxylase in homogenates of adrenal medulla or hypothalamus of rats. It is suggested that inhibition of firing in dopaminergic neurons mediates the suppressant effect of GBL on ethanol preference.     

Effect of protein source in diets fed during gestation and lactation on food intake regulation in male offspring of Wistar rats

We hypothesized that protein source in the nutritionally adequate AIN-93G diets fed during gestation, lactation, and weaning influences food intake (FI) regulation in male offspring of Wistar rats. Pregnant rats were fed the recommended casein-based (C) or soy protein-based (S) diet during gestation (experiment 1) or during gestation and lactation (experiment 2). Pups (n = 12 per group) weaned to C or S diets were followed for 9 wk (experiment 1) or 14 wk (experiment 2). At termination, body weight was 5.4% and 9.4% higher, respectively, in offspring of dams fed the S diet. Altered FI regulation was shown by failure of devazepide (a CCK-A receptor blocker) to block FI reduction after protein preloads in offspring of S diet-fed dams, whereas it had a strong effect on offspring of C diet-fed dams (P < 0.005). Similarly, naloxone (an opioid receptor blocker) blocked FI reduction more after casein than after soy protein preloads (P < 0.01). In experiment 2, offspring of dams fed the S diet had higher hypothalamic gene expression of agouti related protein at weaning (P < 0.05), and higher FI was found throughout postweaning (P < 0.0001). FI reduction after protein preloads at week 7 and after glucose preloads at week 13 was greater in offspring of C diet-fed dams (P < 0.05). Plasma insulin at weaning and insulin, ghrelin, and glucagon-like peptide-1 at week 15 were higher in offspring of S diet-fed dams (all P < 0.05). In conclusion, nutritionally complete C and S diets consumed during gestation and lactation differ in their effects on body weight and FI regulation in the offspring. Extending the diet from gestation alone to throughout gestation and lactation exaggerated the adverse effects of the S diet. However, the diet consumed postweaning had little effect on the outcome.     

Effect of the melanocortin receptor stimulation or inhibition on ethanol intake in alcohol-preferring rats

It has been recently reported that acute intracerebroventricular injection of 1 nmol/rat of the non-selective melanocortin 3 and 4 receptor (MC3/4) agonist MTII reduces ethanol intake in female AA alcohol-preferring rats and alters opioid peptide levels in the ventral tegmental area of rats. To better understand the role of the MC system in the control of ethanol intake, we tested the acute and chronic effects of lateral ventricular (LV) injections of 0.01-1 nmol MTII, of 0.1-1 nmol of the MC3/4R receptor antagonist agouti related peptide (AgRP), and 0.1-0.5 nmol of the MC3/4R receptor antagonist SHU9119 on food, water, and 10% ethanol intake in Marchigian-Sardinian alcohol-preferring (msP) rats, which spontaneously ingest pharmacologically relevant quantities of ethanol both under short and long term access conditions. The data showed that with 2h/day ethanol access, LV MTII injections reduced intake of food and ethanol intakes. When food, water, and ethanol were available ad libitum and 0.01 nmol MTII was given by daily LV injection, however, ethanol intake was reduced for only the first 2 days, whereas food intake was reduced for all 5 days of treatment. Finally, acute LV injection of neither AgRP nor SHU9119 affected ethanol intake under ad libitum conditions, although both antagonists significantly increased food and water intake. In conclusion, these data fail to support a role for endogenous MC3/4R in the control of spontaneous ethanol intake in the msP rat. MC3/4R agonism, however, reduced ethanol intake in association with reduced food intake, suggesting that MTII might reduce nutrient-related controls of ethanol intake rather than, or in addition to, reward-related controls of ethanol intake.     

Effect of nickel on testicular nucleic acid concentrations of rats on protein restriction

The nucleic acids (DNA and RNA) and total protein concentration in testes were estimated in male Wistar strain rats treated intraperitorally with nickel sulfate (2.0 mg/100 g body weight) on alternate days for 10 dosages. In both normal (18% casein) and protein-restricted (5% casein) experimental animals, the nucleic acids and total protein concentration were found to decrease significantly compared to the corresponding controls. Sperm count and sperm motility were also reduced in both experimental groups of animals. The results indicate that nickel influences the expression of genetic information by reducing testicular nucleic acids and protein concentration in both dietary experimental groups.     

Effect of maternal ethanol consumption on foetal and neonatal rat hepatic protein synthesis.

Effects of maternal ethanol consumption were investigated on the rates of protein synthehsis by livers of foetal and neonatal rats both in vivo and in vitro, and on the activities of enzymes involved in protein synthesis and degradation. The rates of general protein synthesis by ribosomes in vitro studied by measuring the incorporation of [14C]leucine into ribosomal protein showed that maternal ethanol consumption resulted in an inhibition of the rates of protein synthesis by both foetal and neonatal livers from the ethanol-fed group. The rates of incorporation of intravenously injected [14C]leucine into hepatic proteins were also significantly lower in the foetal, neonatal and adult livers from the ethanol-fed group. Incubation of adult-rat liver slices with ethanol resulted in an inhibition of the incorporation of [14C]leucine into hepatic proteins; however, this effect was not observed in the foetal liver slices. This effect of externally added ethanol was at least partially prevented by the addition of pyrazole to the adult liver slices. Pyrazole addition to foetal liver slices was without significant effect on the rates of protein synthesis. Cross-mixing experiments showed that the capacity of both hepatic ribosomes and pH5 enzyme fractions to synthesize proteins was decreased in the foetal liver from the ethanol-fed group. Maternal ethanol consumption resulted in a decrease in hepatic total RNA content, RNA/DNA ratio and ribosomal protein content in the foetal liver. Foetal hepatic DNA content was not significantly affected. Ethanol consumption resulted in a significant decrease in proteolytic activity and the activity of tryptophan oxygenase in the foetal, neonatal and adult livers. It is possible that the mechanisms of inhibition of protein synthesis observed here in the foetal liver after maternal ethanol consumption may be responsible for at least some of the changes observed in 'foetal alcohol syndrome'.     

Effect of lithium chloride on ethanol uptake by rats

A selective uptake of ethanol by presenting its 5% solution as the only source of fluid was elaborated in rats for 2 months. It was found that lithium chloride injected intravenously in a dose of 35 mg/kg twice per 24 hours for 14 days depressed the ethanol preference causing a motivation inversion whose mechanism was associated with the changes in the activity of the hypothalamic centres of the neuroendocrine regulation. A possibility of lithium salts in the therapy of chronic alcoholism is discussed.     

Effect of short-term ethanol intake on antibody-dependent cell-mediated cytotoxicity (ADCC) in rats.

The present study was designed to evaluate the effect of short ethanol intake on ADCC activity in blood and spleen mononuclear cells. Wistar rats were fed a standard diet and drank 0.1 M ethanol solution for three days. Glucose and water controls were used in this experiment. Increased ADCC activity was found in ethanol consuming rats in the blood and spleen as compared to both controls. Our findings support the assumption that ADCC may play an important role in liver disease of alcoholics.     

Unpredictable cold-immobilization stress effects on voluntary ethanol consumption in rats

The effects of exposure to a schedule of unpredictable cold-immobilization stress on voluntary ethanol consumption were examined. Following testing for ethanol preference, rats were divided into high, medium and low ethanol consuming groups on the basis of daily ethanol intake (g/kg/day) and exposed to immobilization stress over an 18 day period. Voluntary ethanol consumption was monitored during the stress period and for an additional 36 days post-stress. Results indicated a differential effect of stress on ethanol intake in that low ethanol consuming rats increased their ethanol intake during the stress period and maintained this increase throughout the entire post-stress period as compared to non-stressed controls. High ethanol consuming groups demonstrated a small (marginally significant) decrease in ethanol intake during the stress period as compared to baseline levels. No change in ethanol intake was observed for the medium ethanol consuming groups. The results suggest that unpredictable immobilization stress has a differential effect on ethanol intake depending upon pre-stress levels of ethanol consumption.