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Two hundred and fifty‐six consecutive alcoholics admitted for detoxification, but not having delirium tremens, were evaluated for hypertension. Thirty‐three per cent (84) of the alcoholics had a blood pressure ≥ 160/95 mm Hg on or within 72 hr of admission. In 71% (60 of 84) of alcoholics with hypertension, pressure elevation was transitory, whereas 29% (24 of 84) required therapy. After 4 to 5 days of abstinence, alcoholics with transitory hypertension, whose blood pressure was no longer elevated, had a larger increment of pressure (p amp;lt; 0.001) with a cold pressor test than did normotensive alcoholics. Hypertensive alcoholics were older and tended to use greater amounts of alcohol, but their liver enzymes, alcohol levels on admission, and serum magnesium concentrations did not distinguish them from normotensive alcoholics. Basal plasma renin activity and epinephrine were elevated in both hypertensive and normotensive alcoholics, whereas plasma norepinephrine was normal. Although plasma renin activity (4.08 ± 0.9 vs. 2.88 ± 0.4 ng/ml/hr) and epinephrine (138 ± 17 vs. 108 ± 28 pg/ml) were higher in alcoholics with hypertension than in normotensive alcoholics, differences were not significant. However, elevated plasma epinephrine was found in 86% of alcoholics with hypertension, whereas only 44% of normotensive subjects had elevations (x2= 5.49; p = 0.01). Although alcoholics with hypertension demonstrated an exaggerated catecholamine response with the cold pressor test, these changes per se did not explain the elevations in blood pressure. Thus, a transitory, reactive form of hypertension associated with increased catecholamines and vascular hyperresponsiveness is present in alcoholics.

Since serotonin (5-HT) reportedly is involved in aberrant drinking of ethyl alcohol, the present study examined a possible role of the concentration of 5-HT in systems originating in the dorsal raphe nucleus (DRN), median raphe nucleus (MRN) or both nuclei. The preference for alcohol offered in concentrations increased over 10 days from 3% to 30% was determined for each Sprague-Dawley rat. After the rats were anesthetized with sodium pentobarbital, either 10 microg 5,7-DHT or artificial cerebrospinal fluid (CSF) was micro-injected stereotaxically into the DRN, MRN or both nuclei. After 10 days, a second alcohol preference test was offered to the animals. Then the rats were decapitated, each brain removed, and the block of tissue containing injection sites was saved for histological analysis. The remaining portion was dissected into separate regions for analysis by HPLC of 5-HT, 5-hydroxyindoleacetic-acid (5-HIAA), norepinephrine (NE), dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The 5,7-DHT lesion of the DRN depleted the levels of 5-HT and 5-HIAA by 50-55% in the midbrain and pons and by 70-80% in the frontal cortex, whereas, the 5,7-DHT lesion of MRN reduced 5-HT in all regions except the corpus striatum. The depletion of 5-HT was lower in MRN-lesioned than in DRN-lesioned rats in the frontal cortex and nucleus accumbens. The combined lesion of both DRN and MRN produced a massive decline of >90% of 5-HT and 5-HIAA in all structures except the pons where 5-HT was reduced by 70%. Whereas the level of NE was reduced mainly in the frontal cortex, the levels of DA and its metabolites were essentially unaffected by the 5,7-DHT lesions. Although single or combined lesions of the DRN and MRN failed to alter the intake of alcohol of the rats, the combined serotonergic lesions increased significantly the ingestion of water but not food. Correlational analyses in the sham groups showed a negative association between the intake of alcohol and cortical dopamine and possible hippocampal 5-HT and NE as well as between the ingestion of food and of 5-HT in the frontal cortex. Taken together, these observations in the Sprague-Dawley rat suggest that lower levels of these monoamines in certain regions of the brain may play a role in the maintenance of the basal intake of alcohol but not in the drinking after the injection of 5,7-DHT. Explanations of our findings include: (1) a compensatory neurochemical change in pre- or postsynaptic 5-HT receptors subsequent to the dysfunction of serotonergic neurons in the forebrain; (2) a unique characteristic of the Sprague-Dawley strain of rat; and (3) residual quanta of 5-HT which sustains the pattern of alcohol drinking.

Prenatal ethanol exposure produces severe changes in brain, liver, and kidney through mechanisms involving growth factors. These molecules regulate survival, differentiation, maintenance, and connectivity of brain, liver, and kidney cells. Despite the abundant available data on the short and mid-lasting effects of ethanol intoxication, only few data show the long-lasting damage induced by early ethanol administration. The aim of this study was to investigate changes in nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and vascular endothelial growth factor (VEGF) in brain areas, liver, and kidney of 18-mo-old male mice exposed perinatally to ethanol at 11% vol or to red wine at the same ethanol concentration. The authors found that ethanol per se elevated NGF, BDNF, HGF, and VEGF measured by ELISA in brain limbic system areas. In the liver, early exposure to ethanol solution and red wine depleted BDNF and VEGF concentrations. In the kidney, red wine exposure only decreased VEGF. In conclusion, the present study shows that, in aged mice, early administration of ethanol solution induced long-lasting damage at growth factor levels in frontal cortex, hippocampus, and liver but not in kidney. Otherwise, in mice exposed to red wine, significant changes were observed in the liver and kidney but not in the hippocampus and frontal cortex. The brain differences in ethanol-induced toxicity when ethanol is administered alone or in red wine may be related to compounds with antioxidant properties present in the red wine.

Rats that were selectively bred for differences in alcohol‐induced sleep time (alcohol neurosensitivity) were tested for differences in formation and extinction of alcohol‐ and LiCl‐induced conditioned taste aversions. Male rats bred for high, control, or low alcohol sensitivity (HAS, CAS, and LAS rats, respectively) were deprived of water and given daily 30 min access to water for a baseline period of 7 days. Rats were then given a novel 0.125% sodium saccharin solution, followed by an intraperitoneal injection of either saline, 2 g/kg of ethanol (at 10% w/v), or 50.9 mg/kg of LiCl(0.15 M) on 3 conditioning days. Each saccharin exposure was followed by a recovery day of BCCBSS to water. The ethanol‐induced saccharin aversion extinguished more rapidly in LAS rats than in CAS or HAS rats (p < 0.05), but LiCl conditioned equivalent aversions in each group. Also, ethanol injection results in large differences in observed resting behavior in these rats (HAS > CAS > LAS), but LiCl injection produced no reliable group differences in resting. The weaker alcohol‐Induced M e aversion in LAS rats accords with their previously measured higher oral consumption of alcohol (Kulkosky et al., Alcoholism 17: M‐651, 1993) and the idea that alcohol intake is limited by an expectancy of postingestive consequences. The weaker ethanol induced aversion in LAS rats reflects selective breeding of an alcohol‐specific trait and not a general difference In aversive conditioning or chemical neurosensitivity.

In humans and in animal models the most frequently observed alcohol‐related birth defect (ARBD) is intrauterine growth retardation (IUGR). The central nervous system (CNS) is sensitive to the growth inhibitory effects of in utero ethanol exposure and neonatal CNS alterations with associated behavioral deficits are a likely result of maternal ethanol consumption. Presently, little information exists as to the biochemical mechanism by which ethanol inhibits fetal CNS growth. Further, it is unknown if there are genetic differences in maternal or fetal responses to ethanol. Ongoing research using a chick model indicates that pharmacologically appropriate doses of ethanol (< 30 mm) inhibit brain growth and reduce CNS 3′,5′‐cyclic adenosine monophosphate (cyclic AMP) with an associated 50% decrease in the binding of cyclic AMP by the regulatory subunit (RII) of protein kinase A. Furthermore, there is a specific loss of phosphorylation of RII by kinase catalytic subunit as a result of ethanol exposure. Because tissue cyclic AMP content and the degree of RII phosphorylation are important parameters for the regulation of protein kinase A catalytic activity, it is hypothesized that these alterations may be biochemical transformations that underlie ethanol‐induced growth suppression.

Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.

Young and aged rats were treated chronically with ethanol or scopolamine. Muscarinic receptors were measured in cerebral cortex, hippocampus and striatum. Following scopolamine treatment muscarinic receptor density in cerebral cortex, hippocampus and striatum of young rats increased by 34, 57 and 27%, respectively; in brains of aged rats the increase was 41% in cerebral cortex, 43% in hippocampus and nil in striatum. Affinity of muscarinic receptors was not changed by scopolamine treatment. Following chronic ethanol administration there was a 48% increase in cortical muscarinic receptor density in young, but not aged rats. The density of muscarinic receptors in hippocampus and striatum of both young and aged rats was not affected by ethanol treatment. Affinity of receptors in hippocampus of aged, ethanol-treated rats was increased compared to age-matched controls. Adaptative responses of the muscarinic receptor/transducer system to neurotransmitter availability are present in both young and aged rats, both the ethanol-induced response is present only in young animals. This suggests differences in the mechanism of action of ethanol and receptor agonists and antagonists in modulating receptor plasticity.

This study applied EMG analysis methods to identify muscle group activity profiles and potential overload risks in powered wheelchair use.We quantified muscle effort and fatigue using EMG analysis methods during powered wheelchair manoeuvres by 10 multiple sclerosis patients. Video recordings of the different sub-tasks were related to information on surface EMG amplitude (rectified EMG) and spectral information (Median frequency) from M. trapezius, M. deltoideus (pars medius), M. deltoideus (pars anterior), M. pectoralis, M. biceps, M. triceps, wrist extensors and flexors, using Joint Analysis of EMG Spectrum and Amplitude (JASA analysis).Task durations and subjective data indicated that tasks requiring finer motor control took longer and were perceived as more difficult. Kinesiological functions of all muscle groups identified forward steering to be associated with activation of M. deltoideus (pars anterior), M. pectoralis, M. trapezius and M. deltoideus (pars medius); backwards steering with predominant activation of M. deltoideus (pars medius), M. biceps brachii and wrist flexors; left steering with maximal activation of M. biceps and wrist flexors, and right steering with maximal activation of M. triceps and wrist extensors. These profiles were confirmed in analysis of the functional tasks. JASA analysis documented muscle fatigue in the wrist extensors, whereas increased activation was found in M. trapezius, M. deltoideus (pars anterior) and wrist flexors.EMG based kinesiological analysis gives insight in muscle activity and fatigue during powered wheelchair manoeuvres.