• Energy Research
• Closed Access close
• Restricted close
• Embargo close
• CA close
• AU close
• Neuroscience close

The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered.

Platelet aggregation, secretion of serotonin, and formation of thromboxane B2 induced by platelet-activating factor (1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine) were studied in plasma containing physiological concentrations of ionized calcium in eight alcoholics after cessation of heavy drinking. Responses of platelets of four nonalcoholic volunteers, matched with a subgroup of the alcoholics by age and sex, were also investigated. Aggregation of platelets from alcoholics was significantly less throughout the 6-day detoxification period compared with controls. Secretion of serotonin (5-hydroxy-tryptamine) was negligible and the production of thromboxane B2 was not detectable. Decreased platelet aggregability in response to aggregating agents, including platelet-activating factor, may be important in the development of hemorrhagic complications in alcoholics.

Ethanol preference, a component of alcoholism, has been known for four decades to differ greatly between C57BL/6 and BALB/c inbred mouse strains. For mapping quantitative trait loci (QTLs) that affect ethanol preference, we used a set of B6.C Recombinant QTL Introgression (RQI) strains, which carry about 5% of the donor BALB/cJ (C) genome on a C57BL/6ByJ (B6) background. After characterizing males of the progenitor and RQI strains for variations in ethanol preference, we scanned their genome for polymorphisms at 244 dinucleotide-repeat marker loci known to differ between B6 and C. Because of the introgression of BALB/c-type QTLs onto the B6 background, some strains showed ethanol preference significantly lower or higher than that of the background strain, suggesting that genetic interaction between ethanol preference QTLs and the background can be operative. The genomic region showing the strongest influence on ethanol preference was on mouse chromosome 15, and corresponds to human chr.12q11-q13.

Rats of Sprague-Dawley strain were fed a liquid ethanol diet that was nutritionally balanced and provided 35% of calories as ethanol. Control animals were pair-fed and received the same liquid diet with maltose-dextrins substituting for ethanol. At birth the pups of both the experimental and control groups were fostered by surrogate mothers which received normal rat chow ad libitum. An average of eight alcohol-fed and eight pair-fed pups were killed at 0-1, 5, 7, 10, 14, 21, 28, and 42 postnatal days. The fixed cerebella of these pups was bisected in the midvermal plane and one-half was embedded in paraffin and the other in Araldite. Projection drawings of hematoxylin and eosin-stained paraffin sections were made at 50X magnification. Using the graphics plate of an Apple II computer, the circumference and area of the vermal cerebellum was determined. We found that at all the time sequences studied the area and circumference of the cerebellum were significantly reduced in ethanol-exposed pups compared with the pair-fed controls.

Mechanisms underlying differential sensitivity to behavioural sensitization to ethanol (EtOH) remain poorly understood, although accumulating evidence suggests a role for glutamatergic processes in the ventral striatum. Efforts to address this issue can benefit from the well-documented fact that in any given cohort, some of the mice (High sensitized; HS) show robust sensitization, while others (Low sensitized; LS) show little, if any, sensitization. Here, we examined whether this variability might be differentially associated with nucleus accumbens (NAc) glutamate processes. Male DBA mice received 5 EtOH (2.2g/kg) or saline injections twice a week and were challenged with EtOH (1.8g/kg) 2 weeks after injection 5. When an EtOH challenge was administered 2 weeks following the induction of sensitization, HS, but not LS, mice showed a robust increase in glutamate levels (67%, P<0.01) as measured by in vivo microdialysis. In a separate cohort, the mGlu2/3 agonist LY354740 (10mg/kg), given prior to the EtOH challenge, abolished the expression of sensitization. To ascertain whether enhanced release could also be observed during the induction of sensitization, glutamate levels were measured after the 1st and 5th EtOH injection and were found to be unchanged in HS mice, although briefly elevated in LS mice at injection 5. To further assess possible glutamate involvement during the induction of sensitization, sensitizing EtOH injections were co-administered with NMDAR antagonists. At the doses used, MK-801 (0.25mg/kg) and CGS 19755 (10mg/kg) blocked the expression of sensitization, but did not significantly interfere with the development of EtOH sensitization. Within the limitations of the present design, the results suggest an important role for EtOH-induced glutamate release in the NAc when sensitization is well established, but not necessarily during the development of sensitization.

Prenatal ethanol exposure can damage the developing nervous system, producing long-lasting impairments in both brain structure and function. In this study we analyzed how exposure to this teratogen during the period of brain development affects the intracellular redox state in the brain as well as the development of anxiety- and depressive-like phenotypes. Furthermore, we also tested whether aerobic exercise might have therapeutic potential for fetal alcohol spectrum disorders (FASD) by increasing neuronal antioxidant capacity and/or by alleviating ethanol-induced behavioral deficits. Sprague-Dawley rats were administered ethanol across all three-trimester equivalents (i.e., throughout gestation and during the first 10 days of postnatal life). Ethanol-exposed and control animals were assigned to either sedentary or running groups at postnatal day (PND) 48. Runners had free access to a running wheel for 12 days and at PND 60 anxiety- and depressive-like behaviors were assessed. Perinatal ethanol exposure resulted in the occurrence of depressive and anxiety-like behaviors in adult rats without affecting their locomotor activity. Voluntary wheel running reversed the depressive-like behaviors in ethanol-exposed males, but not in ethanol-exposed females. Levels of lipid peroxidation and protein oxidation were significantly increased in the hippocampus and cerebellum of ethanol-exposed rats, and there was a concomitant reduction in the levels of the endogenous antioxidant glutathione. Voluntary exercise was able to reverse the deficits in glutathione both in ethanol-exposed males and females. Thus, while voluntary physical exercise increased glutathione levels in both sexes, its effects at the behavioral level were sex dependent, with only ethanol-exposed male runners showing a decrease in depressive-like behaviors.

A decline in walking capacity and high energy cost can limit mobility following stroke. Mechanical energy exchange between lower limb and trunk segments can reflect gait inefficiencies, but reveals little about active energy flow between adjacent segments through muscle actions. This study evaluated mechanical energy expenditures (MEEs) during walking in stroke and healthy groups to understand movement control and explore the impact of walking speed on mechanical energy exchanges.Thirteen adults with hemiparesis and six healthy controls walked at self-selected speed. Power curves for each lower limb joint were segmented into concentric and eccentric sources of muscle power and transfer/no-transfer modes to calculate MEEs during stance.MEEs were lower in the stroke group on the affected side compared to the less affected side and compared to controls. Specifically, the affected plantarflexors transferred less energy distally via concentric action in late stance compared to the less affected side. However, the stroke group generated greater energy at the ankle in the absence of transfer compared to controls. Less concentrically transferred energy through midstance and absorbed in late stance was evident by the knee extensors bilaterally in stroke. At the hip, the total energy (no transfer) was reduced on the affected side. Classifying stroke subjects by walking speed (.6m/s) revealed disruptions in harnessing energy through motion and transfer energy across segments in the slower group.The limited ability of those with stroke to exploit intersegmental energy transfer to optimize efficiency may limit endurance and functional independence.

Stimulation of locomotor activity by low doses of ethanol (EtOH) and the potentiation of this response after repeated administration (sensitization) have been related to EtOH's rewarding and addictive properties and to altered dopaminergic activity in brain. In mice, behavioral sensitization to EtOH occurs only in a subset of treated animals, and this provides an opportunity for distinguishing general drug effects from sensitization-specific brain effects.In view of evidence suggesting a role for dopamine D2 receptors in EtOH preference and abuse liability, the present study addressed the hypothesis that D2 binding would be altered in specific brain regions in mice showing differential sensitization responses to chronic EtOH administration.Male albino Swiss mice received 2.4 g/kg EtOH i.p. daily for 21 days and were then separated into sensitized or non-sensitized subgroups on the basis of weekly locomotor activity tests.Autoradiographic analyses of [(3)H]raclopride binding to D2 sites revealed significant increases in the anterior caudate-putamen of mice in the EtOH-sensitized group when compared with either saline controls (+40%, P<0.00009) or to mice in the EtOH non-sensitized group (+32%; P<0.0003). Smaller increases were seen in the ventrolateral caudate-putamen of sensitized animals (+18% vs. control, P<0.02; and 12% vs. non-sensitized mice, P<0.07). No differences were found in other brain regions, including the nucleus accumbens, olfactory bulb and substantia nigra.The observed increases in D2-receptor binding in circumscribed targets of nigrostriatal projections may reflect either a pre-existing condition in sensitization-prone animals or a selective vulnerability of D2 receptors to chronic EtOH in these animals. In either case, it may be a marker for differential susceptibility to EtOH sensitization.