Rats were maintained on liquid diets as their sole source of calories and fluid for 10, 15, 20, and 30 days. The diets consisted 35-40% of total calories in the form of ethanol. This procedure resulted in substantial ethanol intake leading to behavioral intoxication. Blood ethanol concentrations were found to be elevated throughout the day with a peak during the dark phase of the light cycle. The removal of ethanol resulted in evidence of physiological dependence, including behavioral manifestation of autonomic and somatic dysfunction and an increased susceptibility to audiogenic convulsions. Ten days of ethanol exposure was found to be sufficient for the reliable induction of ethanol dependence. Further increases in ethanol exposure resulted in increased hyperexcitability as measured by susceptibility to audiogenic convulsions. The severity of withdrawal behavior was found to be correlated with the blood ethanol concentration measured upon ethanol removal. A behavioral rating scale for the evaluation of alcohol withdrawal intensity in rats is described.

Animals↗

PubMedDate not supplied

Negative chronotropic effect of chronic ethanol ingestion in the rat.

The chronic consumption of ethanol has been correlated with the development of arrhythmias. This study looked at the effect of chronic ethanol ingestion on the action potential of sino-atrial cells. The studies were carried out on hearts excised from male Long-Evans hooded rats, pair-fed on ethanol (E) or control (C) liquid diet. The ethanol diet supplied 35-39% of calories as ethanol. The studies of isolated sino-atrial tissue were carried out after 18-20 weeks, 30-32 weeks and 40-42 weeks on the diet. Sino-atrial cells from E and C rats were compared for changes in spontaneous rate, action potential amplitude, time to repolarize to -70 mV, and resting membrane potential. At 18-20, 30-32 and 40-42 weeks the spontaneous rate of firing of the sinus node was significantly lower in the E group as was the maximum response to isoproterenol. The time to repolarize to -70 mV was longer in E. The endogenous level of catecholamines was also lower in the E group.

Action Potentials↗

PubMedDate not supplied

Ethanol exposure affects trophic factor activity and responsiveness in chick embryo.

Chick embryos were chronically exposed to either ethanol (approximately 30 mg/d) or saline, from E4-E13. Homogenate extract was prepared from forebrain tissue from E16 experimental and control embryos and was applied to cultured dorsal root ganglia (DRG). Neurotrophic activity in the forebrain extract (FBX) was significantly reduced in the ethanol-treated embryos compared to saline controls, both in terms of influences on neuronal survival and process elaboration. In addition, E8-9 DRGs from embryos exposed to ethanol from E4 were less viable in the presence of NGF than were those from controls. DRG survival in the presence of E16 FBX (from untreated embryos) was not different following ethanol treatment, but neurite production was significantly reduced. These results suggest that neurotrophic factor content and responsiveness may be appreciably altered following chronic prenatal ethanol exposure. Such alteration could underlie certain CNS anomalies seen in the fetal alcohol syndrome.

Animals↗

PubMedDate not supplied

Creatine kinase release from isolated EDL muscles in chronic ethanol-treated rats.

Chronic ethanol abuse has been shown to cause damage to skeletal muscle in animals and patients as reflected by elevated serum levels of cytosolic enzymes and histological examination. The present study investigated the hypothesis that elevated serum creatine kinase levels in ethanol-treated animals vs. sucrose control animals may result from increased enzyme release or efflux from muscle. Creatine kinase release was measured from extensor digitorum longus (EDL) muscles isolated from rats chronically treated for 28 weeks with ethanol and from sucrose fed controls. The in vitro cumulative release of creatine kinase over a 2-h period was significantly higher in the ethanol-treated animals. Consistent with an increased release of enzyme into the bath, creatine kinase levels in muscle homogenates at the end of the incubation period were lower in the ethanol-treated animals. Creatine kinase levels in serum obtained from trunk blood samples were statistically higher in the ethanol-treated animals compared to sucrose controls. These findings demonstrate increased enzyme release from fast-twitch skeletal muscle in chronic ethanol-treated rats.

Animals↗

PubMedDate not supplied

Chronic ethanol alters CNS cholinergic and cerebellar development in chick embryos.

Chick embryos were given daily injections of ethanol (approximately 30 mg/day) either chronically from embryonic days 4 to 15 (E4-E15) or E18, or acutely from E15 to E18. Untreated and saline-injected embryos served as controls. Although morphological indicators of developmental age were not different among groups, chronic ethanol reduced weights of several brain regions. Similar to rodent models of prenatal ethanol exposure, chronic ethanol treatment reduced cerebellar Purkinje cell numbers compared to controls. Chronic but not acute ethanol exposure resulted in a significant reduction in choline acetyltransferase activity in the optic tectum (OT) and forebrain (FB) compared with controls. This study demonstrates that the chick embryo is a viable model to investigate the effects of ethanol exposure on CNS development. Unlike the mammalian fetus, the avian embryo is isolated from maternal interactions and may prove more useful in investigating the mechanisms by which ethanol directly influences brain development.

Animals↗

PubMedDate not supplied

P13-kinase inhibition induces dauer formation, thermotolerance and longevity in C. elegans.

The effects of 2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002), an inhibitor of mammalian phosphatidylinositol 3-OH kinase, was tested on an insulin signaling-like pathway in the nematode Caenorhabditis elegans. Populations of C. elegans were treated with LY294002 at different stages of the life cycle, and its effects on development, thermotolerance and longevity were assessed. At concentrations of 160 microM and above, LY294002 significantly induced both dauer formation and thermotolerance. Treatment of adult worms also resulted in a small, but significant, increase in life span. The results presented are consistent with the view that a neuroendocrine signaling pathway functions in adult worms to determine stress resistance and longevity.

Animals↗

PubMedDate not supplied

Effect of hypoxia on respiratory activity in the foetus.

1. Breathing movements stop soon after the induction of hypoxia in foetal animals, a response attributed to the active inhibition of the respiratory centres. Separate studies using punctate lesions have identified lateral pontine and thalamic sites in foetal sheep from which respiratory inhibition may arise, but whether either of these loci are actually oxygen sensitive or whether they receive input from other regions responsive to hypoxia, has not been established. 2. FOS immunocytochemistry was used to identify neuronal pools activated by hypoxia in the brain of late-gestation foetal and newborn sheep. FOS-positive cells were found in the pons in regions corresponding to the medial parabrachial and Kolliker-Fuse nuclei and were shown to be catecholaminergic. Neurons in this pontine region were also activated by the piperizine drug almitrine, which, like hypoxia, inhibits respiratory output in the foetus but is a respiratory stimulant in the newborn and adult. Because these pontine neurons do not express FOS protein after challenge with hypoxia or almitrine in the newborn lamb, we argue that they are crucial to the hypoxic inhibition of respiratory activity in foetal life. 3. The role of the placenta in determining these foetal responses and how this may change at birth is discussed.

Animals↗