Alcohol and drug research最新文献

The effects of acute administration of ethanol and nicotine either singly or in combination, have been studied on the plasma amino acids levels and certain biochemical and hematological parameters in the rats. Both ethanol and its combination with nicotine produced significant reduction in the levels of a number of amino acids and the total amino acid pool. Only the levels of taurine and hydroxyproline were increased in the ethanol treated rats, whereas its combination with nicotine resulted in markedly elevated levels of hydroxyproline, ornithine and taurine. These changes were also accompanied by a significant rise in blood glucose, ALT, AST, blood urea and uric acid and a significant reduction in the total protein and triglycerides levels. Nicotine by itself produced less profound effect on the plasma amino acids and other biochemical parameters.

Plasma beta-endorphin-like radioimmunoreactivity (BEND) was measured in opiate addicts and controls with an antisera which cross reacted with lipotropin but not with other endogenous opiate peptides. 43 stable male methadone maintained patients had mean BEND of 18 +/- 11 pg/ml. No relationship was found between BEND, and time of day, dose or time since last methadone. Controls had 22 +/- 8pg/ml. 9 hospitalized freshly detoxified male opiate addicts, 7-23 days after last opioid, had BEND of 32 +/- 11 pg/ml. These same took 7 days of 50 mg oral naltrexone (NTX) daily, and repeat BEND was 41 +/- 13 pg/ml, rising in all instances compared to baseline. Ex-addicts after detoxification had high BEND which rose further during a short course of NTX. Methadone maintained patients had normal BEND. These data are consistent with previous animal and human reports of high plasma BEND level with NTX or detoxification.

Handling procedures used for body temperature measurement in rats, such as repeated rectal probing during restraint, raise body temperature in a manner similar to other stressors. Thus, the common use of this procedure to monitor temperature may actually obscure the results of experiments measuring the acute and chronic effects of alcohol. In the present experiment, temperature was continuously monitored with implanted biotelemetric sensors, thus eliminating the need for repeated stressful handling. Handling stress was found to interact with the effects of ethanol intoxication to augment the initial hypothermic effect of ethanol. Moreover, the rate and extent of tolerance development to ethanol-induced hypothermia was enhanced.

Experiments were conducted to determine the hepatic damage of cocaine in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats in terms of serum glutamic-oxaloacetic transaminase (SGOT) activity, liver weight/body weight ratio and hepatic microsomal enzyme activity, i.e., N-demethylase activity or UDP-glucuronyltransferase (GT) activity. In subacute experiments, 2, 4 and 10 daily cocaine treatments elevated the level of SGOT activity and reduced the liver weight/body weight ratio in SHR rats. The ethylmorphine N-demethylase activity and the cocaine N-demethylase activity in SHR rats were significantly greater (31% and 26%, respectively) than those in WKY rats. Ten daily treatments with cocaine diminished the ethyl morphine N-demethylase activity and the cocaine N-demethylase activity in SHR and WKY rats. However, attenuation of 4-nitrophenol GT activity was only observed in SHR rats. In acute experiments, a single dose of cocaine, 40 mg/kg, elevated the SGOT activity in SHR rats and reduced the 4-nitrophenol GT activity in SHR rats, but it did not affect the activities of SGOT and 4-nitrophenol GT in WKY rats. A higher dose of cocaine, 60 mg/kg, elevated the SGOT activity and reduced cocaine N-demethylase activity and 4-nitrophenol GT activity in both SHR and WKY rats. The present studies suggest that N-demethylation of cocaine plays an important role in the hepatotoxicity of cocaine in animals.

The binding of the benzodiazepine [3H]flunitrazepam (FNZ) and the allosteric enhancement of FNZ binding by gamma-aminobutyric acid (GABA) were investigated in brain tissue from short-sleep (SS) and long-sleep (LS) mice, lines selectively bred for differential sensitivity to ethanol. GABA enhanced FNZ binding in a dose-dependent manner in both lines. This enhancement was greater in SS than in LS cortical and cerebellar regions, but did not differ between lines in midbrain or hindbrain regions. In whole brain, no difference was observed between the two lines in the number or affinity of benzodiazepine receptors, as determined by FNZ binding. These results suggest that the nature of allosteric interactions within the GABA-benzodiazepine receptor complex is different for LS and SS mice.

Ethanol (ETOH) exerts a dose-dependent biphasic action on different systems. The deleterious effects of severe drinking are well established. However, little is known about the effects of chronic ingestion of moderate amounts of ETOH. The results presented here are the first obtained in a series of experiments designed to analyze the influence of moderate drinking on cardiac electrophysiology. Rat litter-mates were pair-fed a liquid diet as the only source of food. Rats on ethanol (E) received 14% of total caloric intake of ETOH for an experimental period (EP) of 4, 12, or 24 weeks. The control rats on normal diet (N) received the same diet, except for isocaloric substitution of carbohydrates for ETOH. Diet consumption (DC) and body weight (BW) were measured daily and weekly, respectively. ETOH concentration in blood samples was determined periodically, at random. The animals were decapitated at the end of the EP. The heart was removed, and small right atrial strips were isolated and superfused in a tissue bath with Tyrode's solution at 36 degrees C. Membrane potentials (MP) were measured using intracellular micro-electrodes. DC and BW were the same in E and N during the period prior to ETOH drinking. As soon as ETOH was introduced into the diet, DC became significantly higher in E than in N and remained so throughout the EP. This resulted in an enhanced gain in BW, so that by week 4 and throughout the EP, the BW of E was significantly higher than that of N. Small amounts of ETOH were occasionally found in blood samples from E.(ABSTRACT TRUNCATED AT 250 WORDS)

The interactive effects of caffeine and cigarette smoking were studied in fifteen subjects. Four experimental sessions presented either decaffeinated coffee or caffeinated coffee (containing 150 mg caffeine base), followed 20 min later by a smoking or nonsmoking period (20 min duration). Puffing behavior and end-expired air carbon monoxide concentrations were measured to estimate smoke intake. Subjective reports of arousal and tension, and physiologic measures of heart rate and blood pressure were collected. Subjective arousal showed a highly significant antagonistic interaction between caffeine and smoking; smoking blocked the subjective stimulant effects of caffeine. The only cardiovascular effect noted was an increase in heart rate after smoking. Caffeine did not significantly influence puffing behavior; however, the increase in end-expired carbon monoxide concentration after smoking was greater in the caffeine condition, suggesting subjects inhaled more smoke after caffeinated than decaffeinated coffee.

Pigeons trained to discriminate phencyclidine from saline under a color tracking procedure using second-order schedules were studied over a period of more than 5 years. During this time, many other drugs were studied and a variety of procedural changes were made, yet when phencyclidine discrimination was studied under the same second-order schedule, the phencyclidine generalization curve could be reproduced reliably. When the birds were not tested or given any injections for two months, the typical phencyclidine generalization curve could be generated during the first session that testing resumed. These data illustrate the long term stability of phencyclidine discrimination in the pigeon.

Condensation products (CP) of the ethanol metabolite, acetaldehyde, and endogenous amines, such as dopamine and serotonin, have been proposed to be effectors of some symptoms of chronic ethanol use. Since hemostatic defects are known to occur in chronic ethanol use, the effects of CP on in vitro human platelet aggregation responses induced by several agents were determined. Both isoquinoline and beta carboline type CP significantly inhibited aggregation responses induced by epinephrine, with the concentrations to produce 50% inhibition ranging from 8-347 uM. The beta-carbolines significantly inhibited ADP-induced aggregation and also inhibited aggregation induced by collagen or arachidonic acid, but at high concentrations. Effects on epinephrine aggregation and ADP aggregation were reversible. Potential mechanisms of the inhibitory effects were briefly examined. Concomitant use of the phosphodiesterase inhibitor theophylline potentiated the effect of some but not other CP, possibly indicating an involvement of cyclic AMP. Concomitant use of the non-specific beta-adrenergic inhibitor propranolol had no effect on CP inhibition, indicating that CP probably do not stimulate platelet adenylyl cyclase-coupled beta 2-adrenoceptors. Thus, general inhibition by CP of platelet responses in the circulation is unlikely, except, possibly, for epinephrine-induced aggregation, because of the high concentrations of CP required. However, local regulation of platelet responses by release of stored CP during aggregation is possible since CP are stored in platelet dense granules.