The relationship between waist-to-hip ratio and occupational status and life-style factors among middle-aged male and female Japanese workers.

As a marker of body fat distribution and therefore level of obesity, the waist-to-hip ratio (W:H) is a good indicator of coronary heart disease risk status. The present study investigated the association between occupational status and life-style factors, and W:H of middle-aged Japanese male (n = 2,550) and female (n = 1,283) workers in a metal-products factory. A higher W:H was observed in the management level males as compared with the other male workers and we suggest this was promoted by the sedentary aspect of their work, as well as their higher levels of alcohol consumption and lower levels of leisure-time physical activity. In contrast, a higher W:H was recorded in female labourers, whose work was typically less sedentary as compared with female managers. Life-style factors included in the study were not related to this observation. We conclude that other unmeasured psychosocial factors may be important in promoting higher W:H in female labourers.     

酒精、乙醛对星形胶质细胞膜脂质流动性的影响

应用荧光偏振技术探讨酒精及其代谢产物乙醛对与神经细胞发育分化相关的星形胶质细胞膜脂质荧光偏振度（Ｐｒ）和流动度（ＬＦＵ）的影响。结果表明低剂量酒精、乙醛并不影响星形胶质细胞膜脂荧光偏振度和流动度,而在中剂量以上均可影响星形胶质细胞的Ｐｒ值,导致荧光偏振度降低,而细胞膜脂质流动度增高,均与酒精、乙醛剂量显著相关。同剂量酒精、乙醛对星形胶质细胞作用和流动度增加无显著性差异。但酒精、乙醛均可导致星形胶质细胞膜脂质流动性增加,致使细胞膜的结构改变。     

Effect of nociceptin on alcohol intake in alcohol-preferring rats

The present study investigated the effect of nociceptin (NC), the endogenous ligand of the opioid-like orphan receptor ORL1, on ethanol intake in genetically selected Marchigian Sardinian alcohol-preferring (msP) rats. Acute intracerebroventricular (ICV) injection of 250 or 500 ng/rat of NC, just before access to 10% ethanol (offered 2 h/day), significantly increased ethanol intake. Subchronic (7 days) ICV injection of 500 ng/rat of NC, given just before access to 10% ethanol (for 30 min/day), resulted in a progressive decrease in ethanol consumption. After the end of NC treatment, rats progressively recovered their usual ethanol intake. When NC, 500 or 1000 ng/rat, was tested versus the effect of ethanol in the place conditioning paradigm, NC significantly reduced the increase in time spent in the ethanol-paired compartment after conditioning. This finding suggests that NC reduces the rewarding properties of ethanol in msP rats; thus, they may respond to the acute NC administration by increasing their ethanol intake in an attempt to achieve the usual reinforcing effect of ethanol, whereas subchronic NC treatment may result in extinction of ethanol drinking. The results of the present study suggest that the brain NC mechanisms may represent an interesting target of pharmacological interventions for the treatment of alcoholism. Received: 11 August 1998/Final version: 15 October 1998     

5-HT3 receptor over-expression enhances ethanol sensitivity in mice

 Ethanol sensitivity may play a role in the risk of developing alcoholism. The role of 5-HT₃ receptors in sensitivity to ethanol was assessed in mice over-expressing the 5-HT₃ receptor in the forebrain. Sleep time and ED₅₀ for loss of righting reflex (LRR) were used to assess the effect of a high dose of ethanol in transgenic versus non-transgenic mice. The ED₅₀ for ethanol-induced increase in open field activity was used to measure differences in sensitivity to low dose ethanol. The ED₅₀ for ethanol-induced increase in activity was 41% lower in the 5-HT₃ receptor over-expressing transgenic mice compared to non-transgenic mice. However, 5-HT₃ receptor over-expressing mice did not differ from control mice in ethanol metabolism, ED₅₀ for LRR, and ethanol sleep time. Over-expression of 5-HT₃ receptors in mouse forebrain results in an enhanced sensitivity to the stimulating effects of a low dose of ethanol without altering ethanol sedating effects or ethanol metabolism. These data suggest that 5-HT₃ receptors modulate low dose ethanol sensitivity and may explain why, in previous studies, these mice consume less ethanol. Received: 11 December 1998 / Final version: 24 February 1999     

Effects of opiate antagonist treatment on the alcohol deprivation effect in long-term ethanol-experienced rats

Rationale: Opiate antagonists are promising pharmacotherapeutic agents for the treatment of alcohol dependence, reducing craving and relapse rates in weaned alcoholics. However, preclinical findings indicate that they can also increase ethanol consumption and preference in animals with a strong liking for ethanol, depending on the dose and treatment regimen. Objective: The present study examined the effects of chronic, intermittent and acute opiate antagonist treatment on the alcohol deprivation effect (ADE) in long-term ethanol- experienced rats, which is an animal model of craving and relapse. Methods: Long-term ethanol-experienced rats were either implanted with mini-osmotic pumps delivering 0, 0.5 or 1 mg/kg per hour naloxone (chronic treatment) or received intermittent naltrexone injections (2×5 mg/kg per day SC). Effects of chronic and intermittent treatment on the ADE were studied in a four-bottle home cage drinking paradigm. In a second experiment, long-term ethanol-experienced rats trained in an operant ethanol self-administration paradigm received acute naltrexone treatment (0, 0.1, 1 or 10 mg/kg SC) before a 23-h session either during basal drinking or during the ADE. Results: Chronic naloxone treatment increased ethanol preference during the ADE. Intermittent naltrexone treatment at a dose comparable to the lower dose of chronic treatment moderately attenuated the ADE. Acute naltrexone treatment selectively reduced lever pressing for ethanol both during the ADE and during basal drinking only at the lowest dose, whereas higher doses also suppressed water intake. The ethanol-specific suppressant effect on the ADE was long lasting. Concerning basal drinking, however, naltrexone had a long lasting reductive effect only on lever pressing for water. Conclusions: A low dose of naltrexone and an intermittent treatment regimen seem to be necessary to maintain a specific reduction in ethanol intake in individuals with a high motivation to consume ethanol. These findings are consistent with the notion that, at low doses, opiate antagonists reduce the reward value of reinforcers. Received: 29 September 1998 / Final version: 15 March 1999     

Electrophysiological indices of acute effects of ethanol on involuntary attention shifting

Dose-related effects of ethanol (placebo, 0.30, and 0.60 g/kg) on behavioral and event-related brain potential (ERP) indices of involuntary attention shifting of audition were investigated. ERPs were recorded from 11 healthy social drinkers during a forced-choice reaction-time (RT) task. Subjects were presented with 100 and 200 ms tones (P = 0.50 for each) with a constant inter-stimulus interval (ISI) of 1 s. The task was to press either of two buttons, depending on the tone duration. The majority of the tones (“standards”) were of 700 Hz (P = 0.82). Occasionally, however, the frequency of the tones changed, deviating either slightly (750 Hz), moderately (900 Hz), or widely (1200 Hz; P = 0.06 for each) from the standard frequency. In accordance with previous findings, the task-irrelevant frequency deviations prolonged the RT. This RT prolongation was attenuated by alcohol with the 0.3 g/kg dose, thus suggesting less distraction by irrelevant stimulus deviations under the influence of ethanol. Furthermore, the P3a, reflecting involuntary attention shifting, was suppressed by alcohol even with the 0.3 g/kg dose. These findings demonstrate a detrimental effect of alcohol on involuntary attention shifting, evident with doses considerably smaller than previously described, and still juridically acceptable in road traffic in most countries. Received: 19 December 1997/Final version: 26 May 1998     

Primate vocalizations during social separation and aggression: effects of alcohol and benzodiazepines

The most common group of squirrel monkey vocalizations, peeps, are emitted during different social situations including social separation, affiliative interactions, feeding and aggressive confrontations. The present experiments investigated whether peeps and other vocalizations emitted during different social contexts are pharmacologically altered in a similar manner. First, vocalizations were characterized during (1) social separation in juveniles, and (2) resident-intruder aggressive confrontations between dominant monkeys from different social groups. Then, the effects of alcohol (EtOH) and the benzodiazepine chlordiazepoxide (CDP) on vocalizations during social separation and during aggression were examined. Isolated juveniles emitted only one type of call, the isolation peep. Resident monkeys primarily emitted peeps, but also emitted cackles, chucks, noisy calls and pulsed calls. Aggressive peeps were similar in structure and frequency (kHz) to isolation peeps, but were shorter in duration. At the same doses, both CDP (0.3–3 mg/kg) and EtOH (0.1–1.0 g/kg)reduced explosive motor behaviors and isolation peeps in juvenile monkeys during social separation andincreased threat displays and aggression peeps in resident monkeys during confrontations with an intruder monkey from a different social group. Thus, similarly structured vocalizations that were emitted during social separation and aggression were very sensitive to EtOH and CDP, but the social context determined the direction and magnitude of effects.     

Risk factors for orofacial and limbtruncal tardive dyskinesia in older patients: a prospective longitudinal study

Although there is a consensus that orofacial and limbtruncal subtypes of tardive dyskinesia (TD) exist and may represent distinct pathophysiologic entities, few studies have examined the incidence of and risk factors associated with the development of these TD subtypes. Two hundred and sixty-six middle-aged and elderly outpatients with a median duration of 21 days of total lifetime neuroleptic exposure at study entry were evaluated at 1- to 3-month intervals. Using mild dyskinesia in any part of the body for diagnosis of TD, the cumulative incidence of orofacial TD was 38.5 and 65.7% after 1 and 2 years, respectively, whereas that of limbtruncal TD was 18.6 and 32.6% after 1 and 2 years. Preclinical dyskinesia was predictive of both orofacial and limbtruncal TD. History of alcohol abuse or dependence was a significant predictor of orofacial TD only whereas tremor was a significant predictor of limbtruncal TD only. Findings support suggestions that orofacial and limbtruncal TD may represent specific subsyndromes with different risk factors.     

E. coli endotoxin enhances cardiomyopathy in rats with chronic alcohol consumption

The purpose of the study was to show whether it was possible to produce alcoholic cardiomyopathy by short-term alcohol ingestion combined with an infinitesimally low endotoxin injection. Wistar rats were fed an alcoholic liquid diet according to the formula of Lieber and Decarli, and challenged with an injection ofE. coli lipopolysaccharide (LPS) endotoxin (1.0 g/g body weight per day for ten weeks). After ten weeks alcohol diet combined with LPS challenge, light microscopical examination showed changes commonly seen in alcoholic cardiomyopathy such as hypertrophy, oedema and disarray of myofibers. By electron microscopy, degeneration of mitochondria and degeneration of myocardial fibers were observed, the latter showing disturbance of the myofibrilla arrangement and interstitial fibrosis. Rats on an alcoholic liquid diet and rats challenged with a single identical doses of LPS did not show characteristic histological findings of alcoholic cardiomyopathy. These results suggest that short-term alcohol ingestion combined with an infinitesimally low endotoxin injection experimentally produces alcoholic cardiomyopathy, and may support the idea that endotoxin plays an important role in the aetiology of alcoholic cardiomyopathy.     

Experimental analysis of the ‘happy hour’: Effects of purchase price on alcohol consumption

An experimental analogue of a discount drink policy known as the happy hour was used to study the effects of purchase price on drinking behavior. Male volunteers with a prior history of either casual (N=20) or heavy (N=14) drinking were given free access to beverage alcohol during a 20-day period. Approximately half the subjects could purchase alcohol under a single-price condition (50 ¢/drink), while a matched group was given a price reduction daily (25 ¢/drink) during a three-hour period in the afternoon. The results demonstrated that the afternoon price reduction significantly increased alcohol consumption in both casual and heavy drinkers. Reinstatement of the standard purchase price effectively suppressed drinking in both groups. The findings are discussed in terms of the theoretical and research implications of environmental influences on drinking.