摘要:

The vasopressin analog desglycinamide‐(Arg8)‐vasopressin (DGAVP) has been reported to reduce the acquisition of heroin and cocaine self‐injection behavior in rats. This led to the hypothesis that DGAVP can reduce the self‐administration of psycho‐active drugs (including ethanol) by attenuating central reinforcement processes. Under forced ingestion conditions, DGAVP has been reported, however, to enhance alcohol drinking in rats. We studied the effect of DGAVP on the acquisition of voluntary, free‐choice alcohol drinking in naive rhesus monkeys, that had concurrent access to either 1% and 2% (n = 12) or to 4% and 8% (n = 8) ethanol/water solutions in addition to drinking water. Half of the monkeys were injected twice per day with 50 μg. kg‐1of DGAVP for 14 successive days, the other half received placebo. Subsequently, all subjects had access to the same solutions for another 14 days without treatment. DGAVP did not significantly affect concentration preference behavior. With regard to net ethanol ingestion in animals drinking 1% and 2% solutions, DGAVP decreased net ethanol intakes, having a time‐dependent and long lasting effect; placebo‐treated animals gradually increased net ethanol intakes over time. The placebo‐treated animals in the 4% and 8% group, showed a different acquisition pattern; DGAVP reduced net ethanol intake in two animals in a similar way as above. Two animals behaved differently. It is concluded that in a free‐choice condition DGAVP did not enhance the acquisition of alcohol drinking in monkeys, but rather inhibited ethanol self‐administration in the

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00520.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Alcohol preference and hepatic alcohol dehydrogenase activity in adult rats are known to be sexually dimorphic. Intrauterine sibling contiguity (the intrauterine position of a fetus relative to adjacent siblings of the same or opposite sex) alters selected reproductive, behavioral and enzymatic sexual dimorphisms via intersibling sex hormone transfer. We postulated that sibling contiguity would affect alcohol preference and hepatic alcohol metabolism in adult rats. The results of our study demonstrate that adult mMm male Long–Evans rats (genetic male rat developing in utero between two male siblings) had significantly lower ethanol preference, attained higher blood alcohol levels after standard ethanol “challenge” doses and had significantly lower hepatic alcohol dehydrogenase activity than either male siblings developing in utero between two females (fMf) or genetic females developing between two males or between two females (mFm or fFf). Hepatic cytosolic aldehyde dehydrogenase activity was higher in adult female than male rats regardless of nearest neighbor siblings. It is suggested that the differences in ethanol preference and hepatic alcohol dehydrogenase activity between the adult mMm and fMf male rats is due to differences in prenatal hormonal environment which can modulate sexual dimorphisms in alcohol intake and metabolism in the

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00521.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The main objective of this study was to determine whether the activation of dopaminergic pathways, through adrenal‐caudate transplantation, stimulated the production of dopamine and salsolinol in cerebrospinal fluid (CSF) of patients with Parkinson's disease. Dopamine sulfate and salsolinol sulfate in CSF specimens were measured by radioenzymatic technique. The results of this study demonstrated that the replacement of degenerative nigrostriatal neurons with new dopamine‐producing cells by adrenal brain transplants in patients with Parkinson's disease resulted in significant increase (p<0.05) in CSF levels of free dopamine, dopamine sulfate, free salsolinol, and salsolinol sulfate as compared with preoperative levels. Moreover, the oral administration of L‐dopa to these transplanted patients caused substantial (p<0.001) elevation in CSF levels of free dopamine (before L‐dopa, 146 ± 57 pg/ml; after L‐dopa, 575 ± 207 pg/ml), dopamine sulfate (before L‐dopa, 1966 ± 945 pg/ml; after L‐dopa, 41679 ± 29326 pg/ml), free salsolinol (before L‐dopa, 43 ± 29 pg/ml; after L‐dopa, 186 ± 90 pg/ml), and salsolinol sulfate (before L‐dopa, 405 ± 477 pg/ml; after L‐dopa, 2908

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00522.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

We studied the effect of acute exposure, by constant intravenous infusion, to a low blood ethanol concentration (range 8‐14 mmol/l) on the in vivo capacity of urea‐N synthesis (CUNS), alanine elimination, and the nitrogen retention in fed and fasted rats. Alanine was infused to obtain a constant blood concentration of a‐amino nitrogen between 7.3 and 11.7 mmol/1, at which concentrations urea synthesis is at maximum.CUNS was calculated after nephrectomy as accumulation of urea in body water, elimination of alanine as alanine infusion rate corrected for accumulation, and nitrogen retention as the difference.In the fed state ethanol decreased CUNS from 7.84 ± 0.32 μmol N/(min 100 g body weight (BW)) (mean ± SEM) (n = 7) to 6.30 ± 0.58 (n = 6) (p<0.001) and in the fasted state from 8.25 ± 0.27 μmol N/ (min 100 g BW) (n = 10) to 6.90 ± 0.25 (n = 10) (p<0.001).In the fed state ethanol increased the elimination of alanine from 6.49 ± 0.28 μmol/ (min 100 g BW) (n = 7) to 6.95 ± 0.25 (n = 6) (p<0.01), and in the fasted state decreased it from 6.25 ± 0.12 μmol/ (min 100 g BW) (n = 10) to 5.67 ± 0.20 (n = 10) (p<.001).In the fed state nitrogen retention was changed by ethanol from‐1.35 ± 0.53 μmol/ (min 100 g BW) (n = 6) to 0.65 ± 0.77 μmol/(min 100 g BW) (n = 7) (p<0.001), and in the fasted state from‐2.0 ± 0.27 μmol/(min 100 g BW) (n = 10) to‐1.23 ± 0.30 μmol/(min 100 g BW) (n = 10) (p<0.001).The effects of acute exposure to low ethanol concentration on CUNS and nitrogen retention were abolished in rats pretreated with methylene blue.It is concluded that acute exposure to low ethanol concentrations transiently leads to suppression of the capacity of urea synthesis, presumably due to the decrease in NAD/NADH ra

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00523.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Response differences following administration of alcohol between adult males with a positive (FHP) versus negative (FHN) family history of alcoholism have been demonstrated in previous research and are thought to be related to risk for developing alcoholism. If this is so, the pharmacological breadth of addiction risk conferred by a positive family alcoholism history might be studied by determining whether FHP subjects show different responses than FHN to drug classes other than alcohol. We have previously reported on the acute effects of ethanol as compared with secobarbital in FHP and FHN subjects and found that FHP subjects showed greater sensitivity across a variety of subjective measures than FHN subjects for both drug classes. The data reported here are based on an extended data collection period of 3 to 18 hr postingestion, following completion of the acute laboratory portion of the study. Specifically, in the present study, dose‐effect timecourse functions for a variety of physiological (heart rate, blood pressure, and breath alcohol level), subjective (analog mood, drug effect, and withdrawal, Subjective High Assessment Scale (SHAS)), and psychomotor measures (Digit Symbol Substitution Test and numeric recall) were examined in FHP and FHN college‐aged males for secobarbital (0, 100, 200 mg daily) and ethanol (1g/kg daily). FHP and FHN subjects were matched on light‐to‐moderate drinking patterns, anthropometric dimensions, age, years of schooling, and drug use. FHP subjects reported more extended intoxication and greater withdrawal effects following both ethanol and the high dose of secobarbital than did FHN subjects. In addition, these intoxication and withdrawal effects reported by FHP subjects persisted longer than effects reported by FHNs; this was true both for ethanol and the higher secobarbital dose. No differences in physiological responses emerged between the two groups in any drug condition. The present study is the first demonstration of extended intoxication and withdrawal differences between these groups and points to the need to further examine extended time periods following drug ingestion, as this may reveal additional parameters across which these family history groups

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00524.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Self‐ and observer‐rating scales were administered to alcohol‐dependent inpatients during acute withdrawal and regularly for 3 weeks. Following a structured diagnostic interview (SCID) at the end of the 3rd week of hospitalization, subjects were divided into two groups: a dual‐diagnosed group (alcohol dependence and anxiety disorder) and an alcohol‐only group (no other current Axis I diagnosis). The results demonstrated that the dual‐diagnosed subjects experienced higher anxiety levels during and after acute alcohol withdrawal. All rating scales (i.e., Sheehan Patient Rated Anxiety Scale, Spielberger State Anxiety Inventory, Zung Rating Scale for Anxiety, and Hamilton Rating Scale for Anxiety) were analyzed to obtain the best combination of sensitivity and specificity. Taken together, the results indicate that it may be possible to identify alcoholics who require additional psychiatric evaluation early in treatment. This would allow a treatment plan which could be used to address both psychiatric and substance abu

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00525.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

The purpose of this investigation was to determine the effect of various acute doses of ethanol (1.0,3.0,4.0 g/kg) on the distribution of cardiac output (%CO) and blood flow to the splanchnic vascular bed in conscious male Wistar rats. Regional blood flow and cardiac output (CO) were measured by the reference microsphere technique. Mean arterial pressure and CO were significantly reduced 60 min after 3.0 g/kg and 4.0 g/kg of ethanol, while no changes occurred over time in total peripheral vascular resistance or heart rate. Acute ethanol administration produced an early non‐sustained increase in portal vein blood flow, that was most pronounced after a low dose of ethanol, and was attenuated after the 3.0 g/kg and 4.0 g/kg doses of ethanol. The early increase in portal vein blood flow produced a corresponding increase in total liver blood flow. Additionally, we found increases in hepatic arterial blood flow after the higher doses. The combined increase in portal vein and hepatic arterial supply to the liver may serve to increase oxygen delivery, more than the singular increase in portal vein blood flow. This early increase in total liver blood flow after high doses of ethanol may be important for protecting hepatocyte function in the presence of high blood ethanol level

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00526.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

Rats were maintained on liquid diets containing ethanol (35% of total calories) or an equicaloric volume of sucrose instead of ethanol for 10 wk. Vascular strips of isolated rat aortas were mounted in organ chambers to record isometric tension. Ethanol in vitro inhibited the endothelium‐dependent relaxation responses to acetylcholine and ATP in both pair‐fed control and ethanol‐fed rats. The inhibitory effect of ethanol was greater in the pair‐fed rats. In addition, the magnitudes of these relaxation responses in the absence of ethanol in vitro in pair‐fed rats were similar to those in the presence of ethanol in ethanol‐fed rats. In the absence of ethanol in vitro, the relaxations in response to acetylcholine and ATP in the ethanol‐fed rats were greater than in the pair‐fed rats. These results suggest that chronic ethanol consumption can induce tolerance to ethanol‐induced inhibition of endothlium‐dependent relaxation responses to acetylcholine and ATP, and that the relaxations can become adapted to the presence of plasma levels of ethanol, which may inhibit the relaxation in vivo. The augmented relaxation in the ethanol‐fed rats may result from the mechanism causing tolerance to the inhibit

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00527.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

In man, acute ethanol administration decreases lower esophageal sphincter pressure (LESP), prolongs the duration, and lowers the amplitude of esophageal contractions. These changes may contribute to gastroesophageal reflux and esophagitis. To evaluate the underlying mechanisms of these changes an animal model is needed. Hence, we studied the effect of various doses of ethanol on esophageal motility in cats, an animal with an esophagus similar to man's. Similar to man, intravenous administration of ethanol significantly decreased LESP and amplitude of lower (smooth muscle portion) esophageal contractions. It also prolonged the duration of lower esophageal contractions, even through it had no effect on contraction velocity. The effect of ethanol on upper (striated muscle portion) esophagus was different. Ethanol had no effect on the amplitude of contractions, whereas it prolonged their duration and decreased their velocity. The effect of acute ethanol on LESP in four withdrawing alcoholic cats was similar to controls. However, the acute effect of ethanol on the esophageal contractions was less marked in alcoholics. Bilateral cervical vagotomy and intravenous injection of the neurotoxin tetrodotoxin before the administration of ethanol did not prevent the effect of ethanol on LESP. This data suggests that cat esophagus is a good model for studying the underlying mechanisms of the effects of acute ethanol because its response is similar to the esophagus of man, and the acute effect of ethanol on LESP is not neurally mediated but is the result of its direct effect on muscle.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00528.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

We examined the hypothesis that genetically determined differences in sensitivity to alcohol explain some of the genetic variation in alcohol consumption pattern. Self‐report data on average weekly alcohol consumption and self‐ratings of intoxication after a standard dose of ethanol (0.75 g/kg body weight), used as an index of sensitivity, were obtained on 206 Australian twin pairs. Significant genetic covariance between weekly consumption and level of intoxication after alcohol intake was found in males, lower ratings of intoxication being associated with increased consumption. However, when direction of causation models were fitted to the male twin data, the hypothesis that decreased sensitivity was a cause of increased consumption was rejected. The major causal effect was that of weekly consumption on level of sensitivity. A similar, although nonsignificant, trend was observed in females. The strength of the association between self‐report of average weekly consumption and level of intoxication after a standard dose of alcohol supports the validity of the former me

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1991.tb00529.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY