• Energy Research
• Closed Access close
• Restricted close
• Embargo close
• CA close
• Neuroinformatics 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.

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.

The effect of N-methyl-D-aspartate (NMDA) antagonists [dizocilpine, (+)MK-801, and ketamine], an NMDA agonist (D-cycloserine) and of brain serotonin (5-HT) depletion with p-chlorophenylalanine (p-CPA) on acute tolerance to ethanol was examined, using the tolerance model proposed by Radlow [Psychopharmacology 114 (1994) 1-8] and Martin and Moss [Alcohol Clin Exp Res 17 (1993) 211-216]. This model is based on the concept of a linear increase of acute tolerance with time; the rate of acute tolerance development is the slope of the output function that relates blood alcohol concentrations (BACs) and intoxication. Pretreatment with NMDA antagonists inhibited the development of acute tolerance to ethanol, whereas pretreatment with D-cycloserine enhanced it. Depletion of 5-HT by p-CPA also blocked acute tolerance to ethanol. These results on acute tolerance are similar to those previously found on rapid and chronic tolerance to ethanol.

Reactive oxygen species (ROS), although implicated in morphological birth defects caused by ethanol (EtOH) during pregnancy, have not been directly linked to its behavioral deficits. To determine this, a pathogenic oxidative DNA lesion was measured in fetal brain, and a passive avoidance learning test was assessed postnatally in the progeny of CD-1 mice treated once on gestational day 17 with 4g/kg EtOH or its saline vehicle, with or without pretreatment with the free radical spin trapping agent α-phenyl-N-tert-butylnitrone (PBN; 40mg/kg). EtOH-exposed CD-1 progeny, unlike C57BL/6 progeny, had no morphological birth defects, but exhibited a learning deficit at 12 weeks of age (p<0.001), which continued to 16 weeks in males (p<0.01). Peak blood EtOH concentrations were 2.5-fold higher in C57BL/6 mice compared to CD-1 mice given the same dose. PBN pretreatment of CD-1 dams blocked both EtOH-initiated DNA oxidation in fetal brain (p<0.05) and postnatal learning deficits (p<0.01), providing the first direct evidence for ROS in the mechanism of EtOH-initiated neurodevelopmental deficits.

The physiological effects of alcohol are known to include drunkenness, toxicity, and addiction leading to alcohol-related health and societal problems. Some of these effects are mediated by regulation of expression of many genes involved in alcohol response pathways. Analysis of the regulatory elements and biological interaction of the genes that show coexpression in response to alcohol may give an insight into how they are regulated. Fifty-two ethanol-responsive (ER) genes displaying differential expression in mouse brain in response to acute ethanol exposure were subjected to bioinformatics analysis to identify known or putative transcription factor binding sites and cis-regulatory modules in the promoter regions that may be involved in their responsiveness to alcohol. Functional interactions of these genes were also examined to assess their cumulative contribution to metabolomic pathways. Clustering and promoter sequence analysis of the ER genes revealed the DNA binding site for nuclear transcription factor Y (NFY) as the most significant. NFY also take part in the proposed biological association network of a number of ER genes, where these genes interact with themselves and other cellular components, and may generate a major cumulative effect on apoptosis, cell survival, and proliferation in response to alcohol. NFY has the potential to play a critical role in mediating the expression of a set of ER genes whose interactions contribute to apoptosis, cell survival, and proliferation, which in turn may affect alcohol-related behaviors.

Electroencephalographic (EEG) electrodes and ventricular cannulae were implanted in 8 rabbits and 12 rats. Two anti-cholinergic agents, atropine sulfate and scopolamine hydrobromide, were given systemically (1-50 mg/kg) and intraventricularly (5-800 mug). Systemic but not intraventricular injections blocked sensory stimulation-induced or eserine-induced neocortical desynchronization and hippocampal RSA in rats and rabbits which were immobile and either undrugged or ethanol intoxicated. Systemic injections also blocked hippocampal RSA but not neocortical desynchronization in rats given sensory stimulation under urethane anaesthesia, while intraventricular injections only reduced RSA amplitude. Neither systemic nor intraventricular injections blocked neocortical desynchronization or hippocampal RSA recorded from animals when they walked in a motor driven wheel. These experiments support the hypothesis that there are two types of neocortical desynchronization and hippocampal RSA, one cholinergic and one non-cholinergic. They also suggest that atropine and scopolamine pass more readily to the neural system responsible for cholinergic EEG activity from the capillary bed than from the ventricular fluid.

In Raphael’s “Vision of a Knight” (http://www.nationalgallery.org. uk/paintings/raphael-an-allegory-vision-of-a-knight), a sleeping figure dreams of the two paths offered to him. On the left is Virtue, with a long winding road leading up to a castle representing earthly success; on the right is Pleasure, holding a flower. He must choose between immediate reward versus hard work and the promise of future riches. Although Raphael’s knight appears anything but conflicted, the type of self-control he faces is felt to be mentally demanding. The notion of self-control is paradoxical because it implies that there are two “selves.” However, it is ubiquitous in art, psychology, and neuroscience, likely because we all experience it regularly. Self-control feels effortful. The experience of impulses needing to be reigned in is familiar to the shopper, the dieter, the addict, and the student faced with homework. Plato viewed the soul as a chariot pulled by winged horses (the passions) and controlled by a driver (reason), and the notion of a conflicted self has found expression in almost all conceptions of human behavior since then, up to modern psychology, economics (1), and cognitive neuroscience. Most dual-systems accounts suggest the existence of one system that makes decisions rapidly and automatically and is especially influenced by emotional processes such as reward anticipation and one system that is more deliberate and incorporates long-term goals. Some models have the more deliberative system inhibiting reward-seeking drives. Impulsivity, a tendency to act rashly without consideration of consequences, would be the interaction of strong incentive drive with impaired (or weak) inhibition. Perhaps the most obvious expression of this model is drug addiction, where it literally seems as if there are two competing desires: one for the drug and one for abstinence, with their interaction experienced as conflict. Vulnerability to addiction is often conceptualized as an interaction between an enhanced incentive response to drug use opportunities (including cues) and reduced self-control. These cognitive functions are linked to two sets of brain structures: targets of mesolimbic dopamine (nucleus accumbens, amygdala, insula, orbitofrontal cortex) for reward and motivation and lateral prefrontal cortex and anterior cingulate cortex (ACC) for self-control. A third set of regions, referred to as the salience network and centered in the anterior insula and ACC, may be implicated in coordinating or switching between the two systems (2). Converging evidence linking poor inhibitory control to substance use comes from several research domains, including personality research (3), cognitive neuroscience, and brain imaging. Personality research has identified an externalizing spectrum, characterized by persistent difficulty in controlling impulses, which underlies several conceptually linked syndromes, such as alcohol use disorder (AUD), childhood conduct disorder