Effect of isolation stress on ethanol pharmacokinetics in the blood of rats developing a taste for alcohol and in the stage of physical dependence on alcohol

Head space chromatography was used to study the rate of ethanol excretion as a criterion of the activity of ethanol-oxidizing enzymatic system in rats. Isolation stress was shown to be one of the factors determining inclination to voluntary ethanol intake. The level of alcohol motivation directly correlated with the degree of stress. At the stage of physical dependence on ethanol the activity of ethanol-oxidizing enzymatic system and ethanol consumption were independent of the isolation stress, but related to profound biochemical and neurochemical variations.     

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.     

慢性应激不同方式对大鼠血清皮质酮的影响

目的：比较慢性应激不同方式对生理状态大鼠血清皮质酮水平的影响,研究机体慢性应激反应的整体性适应特征。方法：采用连续4周的适宜游泳、束缚和二者复合的三种应激方式后,测定大鼠血清皮质酮基础含量,分析不同慢性应激方式对皮质酮水平的影响。结果：血清皮质酮水平与对照组比较,复合组无显著性差异;游泳组虽升高但无显著性;束缚组升高有显著性意义。结论：束缚可致大鼠血清皮质酮水平增高;初步认定游泳与束缚复合慢性应激方式可能对机体的整体适应性能具有积极意义。     

Effect of ethanol on heart rate and blood pressure in nonstressed and stressed rats

The effect of ethanol on the cardiovascular system (ECG, heart rate, blood pressure) was studied in anesthetized, nonstressed or stressed rats. In anesthetized rats, ethanol showed no effect on heart rate or ECG. In nonstressed rats, ethanol sedated the animals but increased heart rate significantly. This ethanol induced tachycardia seemed the result of a direct stimulation of the sympathetic nerves to the heart. Blood pressure was not significantly affected by ethanol in these nonstressed rats. In stressed rats, marked behavioral excitation and significant increases in heart rate and blood pressure were noted. Ethanol pretreatment calmed the animals considerably during restraint. Ethanol did reduce slightly the stress-induced tachycardia but markedly reduced or antagonized stress-induced blood pressure increases. No major changes in the ECG were noted during these studies with the exception of a few individual animals which showed pathologic ECG responses to ethanol. These data show that ethanol affects cardiovascular functions differently in anesthetized, nonstressed or stressed rats, and that ethanol can significantly reduce or antagonize stress-induced behavioral excitation, tachycardia and hypertension.     

Effect of social isolation on 24-h pattern of stress hormones and leptin in rats

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.     

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.     

Effect of chronic ethanol consumption on emotional stress in the white rat

Chronic pain emotional stress (PES), paired action of the white noise and electric skin stimulation and chronic (during 7 months) ethanol consumption in white rats were shown to act in the same direction. Hypertension, decrease of respiratory rate and increase of Hildebrandt index were observed as a result of PES, ethanol consumption, and especially under PES during ethanol consumption. Ethanol consumption by the animals led to their growth retardation and increase of the spleen and heart mass. Accidental thymus involution was noted both under ethanol consumption and PES. Activation of lipid peroxidation and decrease of superoxide dismutase activity (of its mitochondrial form especially) as well as of Na+,K+-ATP-ase activity were observed in brain homogenates of the rats after PES, while the general ATP-ase activity remained unchanged. An increase of triiodothyronine level and the tendency to thyroxine level increase as well as a decrease of superoxide dismutase activity were observed in the blood serum of these animals. A tendency towards lipid peroxidation level decrease and to brain superoxide dismutase activity increase, as well as blood antioxidation activity increase (evaluated by transferrin and coeruloplasmin contents and by serum superoxide dismutase activity) and a decrease of thyroxine level were observed as a result of ethanol consumption. The mechanisms are discussed of the "anti-stress" action of short-term ethanol consumption and of the action of its chronic consumption, additive to PES.     

Effect of phenazepam on the ethanol demand of rats]

The new Soviet tranquilizer phenazepam given to rats intraperitoneally at a dose of 1 mg/kg daily was shown to be capable of suppressing ethanol addiction produced by 2-month intake of 5% ethanolic solution as the only source of liquid. The mechanism of this effect is likely to be related to the changes in the activity of the neurosecretory centers of the hypothalamus. The phenazepam in the treatment of chronic alcoholism.     

Effect of in vivo nicotine exposure on chlorpyrifos pharmacokinetics and pharmacodynamics in rats

Routine use of tobacco products may modify physiological and metabolic functions, including drug metabolizing enzymes, which may impact the pharmacokinetics of environmental contaminants. Chlorpyrifos is an organophosphorus (OP) insecticide that is bioactivated to chlorpyrifos-oxon, and manifests its neurotoxicity by inhibiting acetylcholinesterase (AChE). The objective of this study was to evaluate the impact of repeated nicotine exposure on the pharmacokinetics of chlorpyrifos (CPF) and its major metabolite, 3,5,6-trichloro-2-pyridinol (TCPy) in blood and urine and also to determine the impact on cholinesterase (ChE) activity in plasma and brain. Animals were exposed to 7-daily doses of either 1 mg nicotine/kg or saline, and to either a single oral dose of 35 mg CPF/kg or a repeated dose of 5 mg CPF/kg/day for 7 days. Groups of rats were then sacrificed at multiple time-points after receiving the last dose of CPF. Repeated nicotine and CPF exposures resulted in enhanced metabolism of CPF to TCPy, as evidenced by increases in the measured TCPy peak concentration and AUC in blood. However, there was no significant difference in the amount of TCPy (free or total) excreted in the urine within the first 24-h post last dose. The extent of brain acetylcholinesterase (AChE) inhibition was reduced due to nicotine co-exposure consistent with an increase in CYP450-mediated dearylation (detoxification) versus desulfuration. It was of interest to note that the impact of nicotine co-exposure was experimentally observed only after repeated CPF doses. A physiologically based pharmacokinetic model for CPF was used to simulate the effect of increasing the dearylation V_max based upon previously conducted in vitro metabolism studies. Predicted CPF-oxon concentrations in blood and brain were lower following the expected V_max increase in nicotine treated groups. These model results were consistent with the experimental data. The current study demonstrated that repeated nicotine exposure could alter CPF metabolism in vivo, resulting in altered brain AChE inhibition.     

Effect of black cumin (Nigella sativa) on cadmium-induced oxidative stress in the blood of rats

The protective effect of black cumin (Nigella sativa=NS) on cadmium-induced oxidative stress was studied in rats. The rats were randomly divided into three experimental groups: A (conrol), B (Cd treated), and C (Cd+NS treated), each containing 10 animals. The Cd-treated and Cd+NS-treated groups were injected subcutaneously daily with CdCl₂ dissolved in isotonic NaCl in the amount of 2 mL/kg for 30 d, resulting in a dosage of 0.49 mg Cd/kg/d. The control group was injected with only isotonic NaCl (2 mL/kg/d) throughout the experiment (for 30 d). Three days prior to induction of CdCl₂, the Cd+NS-treated group received a daily intraperitoneal injection of 0.2 mL/kg NS until the end of the study. Cd treatment increased significantly the malondialdehyde levels in plasma and erythrocyte (p<0.01 and p<0.05, respectively) and also increased significantly the antioxidant levels (superoxide dismutase, glutathione peroxidase, and catalase) (p<0.05) compared to the control group. Cd+NS treatment decreased significantly the elevated malondialdehyde levels in plasma and erythrocyte (p<0.01 and p<0.05, respectively) and also reduced significantly the enhanced antioxidant levels (p<0.05). Cd treatment increased significantly the activity of iron levels (p<0.05) in the plasma compared to the control group. Cd+NS treatment decreased the activity of iron levels (p<0.05) in the plasma compared to the Cd-treated group. In the control group with no treatment, histology of erythrocytes was normal. In the Cd-treated group, there were remarkable membrane destruction and hemolytic changes in erythrocytes. In the Cd+NS treated group, these changes were less than in the Cd-treated group. Our results show that N. sativa exerts a protective effect against cadmium toxicity.     

Effect of pyrazole on ethanol metabolism in ethanol-tolerant rats.

Adult male rats were pair-fed liquid diets, providing 37% of calories as ethanol or sucrose, for 1 month. Alcohol dehydrogenase (ADH) activity in the cytosol fractions of liver homogenates from the two groups did not differ with respect to total activity per 100 g body weight, Km for ethanol, or Ki for pyrazole. Other rats, fed in the same way, were fasted for 18-24 H, then given an intraperitoneal injection of pyrazole followed 1 h later by an injection of ethanol, 3g/kg. Blood alcohol curves showed an unexplained slower rise to maximum level in the chronic alcohol group. Both groups showed a period of several hours in which the blood alcohol stayed at the respective maximum concentrations, which were higher in the control group. After 7-8h the alcohol concentration began to fall in both groups, significantly more rapidly in the chronic alcohol-fed animals. A kinetic analysis shows that the results are adequately explained by the known effects of pyrazole on the ADH-mitochondrial system. The results are interpreted as evidence against the function of any microsomal ethanol oxidizing system in vivo.     

Effect of Curcuma kwangsiensis polysaccharides on blood lipid profiles and oxidative stress in high-fat rats

We have investigated the protective effect of polysaccharides from Curcuma kwangsiensis (CKP) against oxidative injury in rats fed high-fat diet. The protective effect of CKP was compared with Lovastatin, a well-known antioxidant. Sixty SD rats were used for the experimental study. Oxidative injury was induced by feeding high-fat diet for 3 weeks. The blood profiles, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c) levels during experimental period were significantly increased in untreated model control group, whereas high-density lipoprotein cholesterol (HDL-c) levels and antioxidant enzymes activities significantly decreased in untreated model control group. The levels of TC, TG, LDL-c levels in CKP-treated rats were decreased significantly when compared to the untreated model control group, which were brought down to near normal in CKP-treated group. HDL-c level and antioxidant enzymes activities were found to be significantly increased in serum of CKP-treated group compared to the untreated model control group. The protective effect of CKP against oxidative injury was comparable to that of Lovastatin. Our data suggest that CKP exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the experimental animals against oxidative injury induced by high-fat diet treatment.     

Effect of ethanol on the metabolism of the white blood cells.

Ethanol at a concentration of 40 mg% in the medium was found to inhibit the respiratory uptake of oxygen by polymorphonuclear cells obtained from rat peritoneal fluid. The stimulated oxygen uptake by these cells under conditions of phagocytosis was also inhibited with this concentration of ethanol. The quantities of hydrogen peroxide produced by these cells were also found to have been diminished. The possible significance of these findings is discussed.     

Effect of tranquilizing agents on the blood level of endogenous ethanol in alcoholics

Experiments on alcohol addicts blood were made to study the time course of the endogenous ethanol level after a single administration of mebicar (1.5 g), a derivative of bicyclic bisuria, 50 ml of 5% sodium hydroxybutyric syrup, a derivative of gamma-hydroxybutyric acid, and 20 mg diazepam, a derivative of 1,4-benzodiazepines. The clinical effect was recorded simultaneously. It was established that different tranquilizers stimulate the increase in the endogenous ethanol level as regards the spectrum of psychotropic activity. This effect was the most pronounced with mebicar and to a less measure with diazepam.     

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 ethanol on lipoprotein metabolism in human and animal blood

The amount and composition of human and animal blood plasma lipoproteins have been studied as affected by low temperature and high doses of ethanol. Results are presented. A conclusion about antiatherogenic properties of low doses of ethanol based on the data of its effect on the system of blood lipoproteins cannot be considered completely proved. Reliable interpretation of the results of the ethanol effect on lipoproteins and atherogenesis processes needs the further study of mechanisms of the ethanol effect on the exchange and modification of the basic classes of lipoproteins and their subfractions, many their peculiarities being not studied yet.