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.     

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.     

The behaviour of rats selected for their voluntary ethanol consumption

New strains of rats, preferent (HAP) and non-preferent (NAP) for ethanol were selectively outbred from a Wistar stock. The strains have now been raised to the F13 generation. The F9/10 animals, selected for this behavioural investigation, exhibited a significant phenotypic drinking behaviour and/or ethanol consumption. During a free choice between tap water and 10% ethanol solution (v/v), the mean daily alcohol intake for male and female HAP rats was 8.42 +/- 0.69 g/kg/24 h (n = 20 o) and 11.50 +/- 0.42 g/kg/24 h (n = 20 o), for male and female NAP rats 0.74 +/- 0.09 g/kg/24 h (n = 20 o) and 1.76 +/- 0.20 g/kg/24 h (n = 20 o), respectively. The NAP rats exhibited a strong aversion to the 10% ethanol solution when it was the only source fluid. In the open-field test (OFT), as compared to the NAP rats, male individuals of the HAP strain showed a lower motility in the first minute, in penetration into the inner squares, showed a longer latency to start exploration (latency to leave the center), exhibited larger rearing and grooming activity and shorter latencies to start these activities. The defecation rate was smaller and latency to defecation prolonged. Female HAP rats showed higher activity scores in penetration of outer and inner squares and a shorter latency to start exploration. They also had higher rearing but smaller grooming activity. The females exhibited identical defecation but different urination behaviour in comparison to the males. The time-to-emerge latencies of HAP rats were longer than in NAP individuals.     

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)     

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.     

Different diets and amino acid supplementation do not affect the voluntary consumption of ethanol by rats

The effects of four different diets (control diet: 19.5% protein, 60.5% carbohydrate, 10% fat; diet I: 65% protein, 10% carbohydrate, 10% fat; diet II: 5% protein, 76% carbohydrate, 10% fat; diet III: 20% protein, 69% carbohydrate, 1% fat; diet IV: 69% protein, 15% carbohydrate, 1% fat) and supplementation with 3 amino acids (tryptophan: 150 mg/kg/d; arginine: 400 mg/kg/d; taurine: 380 mg/kg/d) on the voluntary consumption of ethanol were investigated in rats using the 2 bottle method. First, rats received the control diet and diets I, II, III and IV for 20 days with a choice of ethanol for the last 6 days only. Ethanol consumption was similar in all dietary groups. Second, rats received the control diet for 8 days followed by diets I, II and IV for another 8 days. Ethanol was offered throughout both periods. The switch to the special diets did not affect ethanol consumption. Third, rats received a control diet with arginine, tryptophan or taurine added to the drinking fluids for 16 days with a choice of ethanol for the last 5 days; thereafter supplementation stopped but the ethanol choice remained. No difference in the voluntary intake of ethanol was noted but ethanol consumption fell after cessation of arginine supplementation. In conclusion, diets differing greatly in their composition or supplementation with these 3 amino acids did not affect the voluntary choice of ethanol by rats in a significant manner.     

Role of benzodiazepine receptors in realizing the anxiolytic effect of compounds on intact rats and on animals with a physical dependence ethanol

Anxiolytic activity of DSIP, sodium hydroxybutyrate, nicotinoyl-GABA, mebicar, some derivatives of aminoandrostane and beta-carboline was not, like in the case of diazepam and beta C-3CEE, related to benzodiazepine receptors. The degree of the decrease in anxiolytic activity of these compounds did not correspond to increasing Ki binding of 3H diazepam in alcoholic rats.     

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 long-term restriction of protein intake,from gestation onward,on free-choice consumption of ethanol by rats

Long-term (including gestational and lactational) restriction of protein (8% of diet) significantly lowered the absolute and relative consumption of 6% ethanol (EtOH) in a two-bottle, free-choice (H₂O vs EtOH) situation during a 76-day test period. This difference in response between rats fed the low protein diet and those fed an isocaloric normal protein (24%) diet became non-significant in two subsequent 100-day test periods. Statistical analysis of observations on individual performance indicated that regularity, cyclicity, and duration of drinking in each animal was random over all three time intervals for both groups. The early, significantly lower EtOH consumption by the protein-restricted group may be due to a paucity of EtOH-metabolizing enzymes in brain and liver, thereby prolonging the CNS effects of lower doses of EtOH consumed. The disappearance of this difference in subsequent test periods may reflect either a behavioral or metabolic adaptation in the developing protein-deficient rat.     

Effect of lithium on voluntary alcohol consumption by low and high preference mouse strains

Lithium chloride was administered to high (C57/B1) and low (BALB/c) alcohol mouse strains. Experience with alcohol, lithium dosage, frequency of drug administration, concentration of alcohol solution, and sex were varied in four consecutive experiments. In contrast to previous findings no significant effects of lithium administration on alcohol consumption were observed.     

Effect of voluntary exercise on longevity of rats

The purpose of this study was to obtain information regarding the effects of exercise on longevity in rats. The exercise used was voluntary activity wheel running. The runners gradually decreased their running from approximately 4 to approximately 1 mile/day as they aged from 9 to 30 mo. The runners lived slightly but significantly longer than sedentary freely eating controls and sedentary pair-fed controls (1,012 +/- 138 vs. 923 +/- 160 and 928 +/- 186 days) but significantly less long than food-restricted paired-weight sedentary controls (1,113 +/- 150 days). Although the exercise improved survival, it did not result in an extension of life-span. In contrast, the food-restricted paired-weight sedentary rats showed a true increase in life-span. The paired-weight rats also had a significantly reduced incidence of malignancies compared with the other three groups. However, there was no significant difference between the runners and the freely eating or pair-fed sedentary controls in the cause of death. These results provide evidence that exercise improves survival but does not result in an extension of life-span in rats.     

Effect of volatile compounds in grass silage on voluntary intake by growing cattle

Twenty-four low dry matter (DM) silages differing in fermentation quality were harvested at the same time from a crop that consisted mainly of timothy (Phleum pratense), and meadow fescue (Festuca pratensis). The silage samples were analysed by gas chromatography (GC) - mass spectrometry and gas chromatography - flame ionisation detection in order to determine and quantify volatiles present in silage. The voluntary intake of the 24 silages had been measured in a previous feeding trial with growing steers of Norwegian Red. Thirteen esters, five aldehydes, three alcohols, and one sulphide were identified and quantified. A total of 51 variables describing the chemical composition of the silages were included in a partial least-squares regression, and the relationship of silage fermentation quality to voluntary intake was elucidated. The importance of variables describing silage fermentation quality in relation to intake was judged from a best combination procedure, jack-knifing, and empirical correlations of the variables to intake. The GC-analysed compounds were mainly present in poorly fermented silages. However, compared with other explanatory chemical variables none of these compounds was of importance for the voluntary intake as evaluated by partial least-squares regression. A validated variance of 71% in silage DM intake was explained with the selected variables: total acids (TA), total volatile fatty acids (TVFA), lactic acid/total acid ratio and propionic acid. In this study extent (by the variable TA) and type of silage fermentation (by TVFA) influenced intake. Further, it is suggested that by restricting the fermentation in low DM grass silages the potential intake of silage DM is maximised.     

Fish oil up-regulates hepatic autophagy in rats with chronic ethanol consumption

In this study, we examined the regulation of autophagy by fish oil in rats under ethanol-containing diets. Thirty male Wistar rats (8-week-old) were divided into six groups and fed a control diet or an ethanol-containing diet, which was adjusted with fish oil to replace 25% or 57% of the olive oil. After 8 weeks, rats in the E (ethanol diet) group showed the significantly higher plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, protein expression of cytochrome P450 2E1 (CYP2E1), and levels of hepatic inflammatory cytokines. However, all of those items had significantly decreased in the EF25 (ethanol with 25% fish oil) and EF57 (ethanol with 57% fish oil) groups. As to autophagic indicators, protein expressions of mammalian target of rapamycin (mTOR), Unc-51-like autophagy activating kinase 1 (ULK1) and p62 were significantly increased in the E group. Conversely, the protein expressions of light chain 3II (LC3II)/LC3I and Beclin1 were significantly decreased in the E group. On the other hand, protein expressions of phosphorylated Akt, mTOR, ULK1, and p62 were down-regulated, protein expressions of LC3II/LC3I and Beclin1 were conversely up-regulated in the EF25 and EF57 groups. Fish oil activated hepatic autophagy via inhibiting the Akt signaling pathway, which exerted protective effects against ethanol-induced liver injury in rats.     

Effect of substance P on ethanol consumption in subchronically alcoholized rats in the limited scheduled access paradigm

The effect of substance P on alcohol intake was studied in rats using a limited scheduled access paradigm. Ascending doses of substance P (100 and 200 micrograms/kg) were administered intraperitoneally to rats approximately 30 minute prior to their 1-hour-per-day access to alcohol. Each dose was administered for 3 successive days, and the effect of substance P was compared to that of saline solution control. Substance P at the dose of 100 micrograms/kg had no effect on alcohol consumption but significantly decreased the alcohol intake at the dose of 200 micrograms/kg. Thus, substance P reduces the alcohol motivation of rats in a limited scheduled access paradigm.     

Chronic ethanol consumption alters cardiovascular functions in conscious rats

Chronic ethanol intake and hypertension are related. In the present work, we investigated the effect of chronic ethanol (20% v/v) intake for 2, 6 and 10 weeks on basal arterial blood pressure, baroreflex and heart rate levels, as well as on the cardiovascular responses to the infusion of vasoactive agents in unanesthetized rats. Mild hypertension was observed after 2 weeks, 6 weeks or 10 weeks of treatment. On the other hand, no changes were observed in heart rate after long-term ethanol intake. Similar baroreflex changes were observed in 2- or 6-week ethanol-treated rats, and affected all parameters of baroreflex sigmoid curves, when compared to the control group. These changes were characterized by an enhanced baroreflex sympathetic component and a reduction in the baroreflex parasympathetic component. No differences in baroreflex parameters were observed in 10-week ethanol-treated animals. The pressor effects of i.v. phenylephrine were enhanced in 2-week ethanol-treated rats; not affected in 6-week treated animals and reduced in 10-week ethanol-treated rats, when compared to respective control and isocaloric groups. The hypotensive response to i.v. sodium nitroprusside (SNP) was enhanced at all different times of treatment, when compared to respective control and isocaloric groups. In conclusion, the present findings showed increased arterial pressure in the early phase of chronic ethanol consumption, which was consequent of rise in both systolic and diastolic pressures. Ethanol intake affected both the sympathetic and the parasympathetic components of the baroreflex. Vascular responsiveness to the pressor agent phenylephrine was initially enhanced and later on decreased during chronic ethanol intake. Vascular responsiveness to the depressor agent SNP was enhanced during chronic ethanol intake.     

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.     

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.