High Doses Of Ethanol Research Articles

Higher long-lasting ethanol sensitization after adolescent ethanol exposure in mice

Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is a possible consequence of ethanol exposure during adolescence. The aim of this study was to characterize the long-term alterations in the stimulant effects of ethanol and in the rate of ethanol sensitization in mice pre-exposed to ethanol during adolescence in comparison to mice pre-exposed to ethanol in adulthood. Adolescent and adult female Swiss mice were injected with saline or ethanol (2.5 or 4 g/kg) during 14 consecutive days. After a 3-week period of ethanol abstinence, mice were tested as adults before and after a second exposure to daily repeated ethanol injections. All mice pre-exposed to ethanol as adults or adolescents showed higher stimulant effects when re-exposed to ethanol 3 weeks later. However, this enhanced sensitivity to the stimulant effects of ethanol was of significantly higher magnitude in mice repeatedly injected with high ethanol doses (4 g/kg) during adolescence. Furthermore, the increased expression of ethanol stimulant effects in these mice was maintained even after a second procedure of ethanol sensitization. Adolescence is a critical period for the development of a sensitization to ethanol stimulant properties providing that high intermittent ethanol doses are administered. These results might contribute to explain the relationship between age at first alcohol use and risks of later alcohol problems and highlight the dangers of repeated consumption of high alcohol amounts in young adolescents.

Chronic ethanol consumption decreases serum sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice

Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.

Congenital brain serotonin deficiency leads to reduced ethanol sensitivity and increased ethanol consumption in mice

Serotonergic dysfunction has been hypothesized to play an important role in the pathophysiology of alcoholism. However, whether congenital serotonin (5-HT) deficiency leads to increased alcohol consumption or affects ethanol-related behaviors has not been established. Here, we use a transgenic mouse line that expresses a hypofunctional variant of the 5-HT synthesis enzyme, tryptophan hydroxylase 2, to examine the impact of 5-HT deficiency on responses to alcohol. We demonstrate that these 5-HT-deficient transgenic animals (Tph2KI mice) recover their righting reflex more rapidly than wild-type controls following a high dose of ethanol and exhibit blunted locomotor retardation in response to repeated ethanol administration. In addition, compared to WT controls, 5-HT-deficient animals consume significantly more ethanol and exhibit increased preference for ethanol in two-bottle choice tests. Our data also suggest that 5-HT plays a critical role in mediating the effects of ethanol on Akt/GSK3β signaling in the nucleus accumbens. Overall, our results corroborate previous theories regarding the importance of brain 5-HT levels in mediating responsiveness to alcohol and demonstrate, for the first time, that congenital 5-HT deficiency leads to increased ethanol consumption and decreased sensitivity to the sedative-like effects of ethanol, perhaps in part through modulating Akt/GSK3β signaling.

Molecular and behavioral characterization of adolescent protein kinase C following high dose ethanol exposure

Ethanol is commonly used and abused during adolescence. Although adolescents display differential behavioral responses to ethanol, the mechanisms by which this occurs are not known. The protein kinase C (PKC) pathway has been implicated in mediating many ethanol-related effects in adults, as well as gamma-aminobutyric acid (GABA(A)) receptor regulation. The present study was designed to characterize cortical PKC isoform and GABA(A) receptor subunit expression during adolescence relative to adults as well as assess PKC involvement in ethanol action. Novel PKC isoforms were elevated, while PKCγ was lower during mid-adolescence relative to adults. Whole-cell lysate and synaptosomal preparations correlated for all isoforms except PKCδ. In parallel, synaptosomal GABAA receptor subunit expression was also developmentally regulated, with GABA(A)R δ and α4 being lower while α1 and γ2 were higher or similar, respectively, in adolescents compared to adults. Following acute ethanol exposure, synaptosomal novel and atypical PKC isoform expression was decreased only in adolescents. Behaviorally, inhibiting PKC with calphostin C, significantly increased ethanol-induced loss of righting reflex (LORR) in adolescents but not adults, whereas activating PKC with phorbol dibutyrate was ineffective in adolescents but decreased LORR duration in adults. Further investigation revealed that inhibiting the cytosolic phospholipase A2/arachidonic acid (cPLA2/AA) pathway increased LORR duration in adolescents, but was ineffective in adults. These data indicate that PKC isoforms are variably regulated during adolescence and may contribute to adolescent ethanol-related behavior. Furthermore, age-related differences in the cPLA2/AA pathway may contribute to ethanol's age-related effects on novel and atypical PKC isoform expression and behavior.

Build a better mouse model, and the world will beat a path to your door

Build a better mouse model, and the world will beat a path to your door

O6 * FREE ORAL COMMUNICATIONS 6: PSYCHOSOCIAL FACTORS AND ALCOHOL USE DISORDERS

O6 * FREE ORAL COMMUNICATIONS 6: PSYCHOSOCIAL FACTORS AND ALCOHOL USE DISORDERS

Effects of binge drinking on action cascading processes: an EEG study

High-dosage alcohol intoxication (i.e., binge drinking in humans) is an increasingly prevalent problem. Despite the well-known long-term consequences, the acute effects of high-dosage alcohol intoxication on cognitive control processes have not been investigated with respect to neurophysiological changes in humans. We provide insights into the effects of high-dosage ethanol intoxication on action control functions in humans on the basis of neurophysiological (EEG) data. Action control processes were examined in a stop-change task. Based on a detailed analysis of behavioral and electrophysiological data, we demonstrate a specific modulation of action cascading processes. Opposed to commonly held views, high-dosage ethanol intoxication (0.9-1.13 ‰) exerts highly specific effects on cognitive subprocesses mediating action control. If action control processes are performed in succession, intoxicated and non-intoxicated participants perform equally well. However, action control processes become compromised during high-dosage ethanol intoxication, when different response options require processing resources in parallel. Under high-dose ethanol intoxication, subjects are not able to prioritize different response options. We could demonstrate that the effects were of high effect sizes (η (2) = 0.702) and rely more on response selection deficits than on deficits in attentional processing. The changes in response selection processes are mediated via the anterior cingulate cortex. The specificity of the observed effects may be due to a differential involvement of dopaminergic and GABAergic processes in action control and attentional selection processes.

Sensitivity to reinforcer delay predicts ethanol's suppressant effects, but itself is unaffected by ethanol

BackgroundRelative preference for smaller, sooner rewards over larger, later rewards (“delay discounting”) is increased by acute ethanol. Additionally, drug-naïve levels of delay discounting can predict subsequent ethanol consumption. However, it is unknown whether these phenomena are driven by a difference in sensitivity to the reinforcer delay or a difference in sensitivity to the reinforcer magnitude, because typical delay discounting tasks manipulate both parameters simultaneously. MethodsTo disambiguate these factors, two tasks were developed in which animals chose between levers with either different delay contingencies (adjusting delay task) or different magnitude contingencies (adjusting magnitude task). When task performance was stable, rats received ethanol (0, 0.6, and 0.9g/kg, i.p.). ResultsEthanol did not affect sensitivity to delay or sensitivity to magnitude. However, responding was suppressed at the highest dose of ethanol (0.9g/kg). Less suppression was found in animals exhibiting high levels of drug-naïve sensitivity to delay. ConclusionThus, this study suggests that ethanol's effect on standard delay discounting tasks is not due to an alteration in sensitivity to delay or magnitude. Additionally, these data show that animals with high sensitivity to delay are resistant to the behaviorally suppressant effects of ethanol, which suggests that low tolerance for delayed rewards and low sensitivity to the behaviorally suppressant effects of ethanol may partly be driven by the same underlying mechanism.

Effects of different doses of ethanol on sperm parameters, chromatin structure and apoptosis in adult mice

ObjectiveChronic ethanol abuse causes reproductive organ failure and infertility in both humans and laboratory animals. Since sperm has a critical role in reproductive function, the objective of this unique study was to evaluate the effects of different doses of ethanol on sperm parameters, chromatin structure and apoptosis in adult mice. Study designA total of 36 adult male mice were equally divided into four groups. Group 1 received ethanol (10%, v/v) containing saccharin (0.2%, w/v), group 2 received ethanol (5%, v/v) containing saccharin (0.1%, w/v), group 3 was treated with saccharin (0.2%, w/v) and group 4 served as control and fed on basal diet for 35 days. Finally, the left cauda epididymis of each animal was cut and placed in Ham's F10 medium. Retrieved spermatozoa were used to analyze count, motility, morphology and viability. Sperm chromatin condensation and DNA integrity were assessed by five different tests including chromomycin A3 (CMA3), toluidine blue (TB), sodium dodecyl sulfate (SDS), and SCD (sperm chromatin dispersion) and sperm apoptosis was assessed by TUNEL. ResultsFollowing ethanol consumption, the sperm count diminished in the ethanol-treated groups. A decrease in sperm motility and an increase in the rate of morphological abnormalities (coiled and broken tails) were seen in the experimental and saccharin groups in comparison with controls. We showed that ethanol consumption can disturb sperm DNA integrity and chromatin remodeling and it may also induce sperm apoptosis. The rates of sperm apoptosis were 51.57±7.45 and 42.85±6.76 in the high ethanol dose and low ethanol dose groups, respectively. ConclusionThe results showed that alcohol has negative effects on sperm parameters, chromatin/DNA integrity and apoptosis in mice. These alcohol-induced sperm anomalies may be dose-dependent.

The Novel Genetank, a Tumor Suppressor Homolog, Regulates Ethanol Sensitivity inDrosophila

In both mammalian and insect models of ethanol intoxication, high doses of ethanol induce motor impairment and eventually sedation. Sensitivity to the sedative effects of ethanol is inversely correlated with risk for alcoholism. However, the genes regulating ethanol sensitivity are largely unknown. Based on a previous genetic screen in Drosophila for ethanol sedation mutants, we identified a novel gene, tank (CG15626), the homolog of the mammalian tumor suppressor EI24/PIG8, which has a strong role in regulating ethanol sedation sensitivity. Genetic and behavioral analyses revealed that tank acts in the adult nervous system to promote ethanol sensitivity. We localized the function of tank in regulating ethanol sensitivity to neurons within the pars intercerebralis that have not been implicated previously in ethanol responses. We show that acutely manipulating the activity of all tank-expressing neurons, or of pars intercerebralis neurons in particular, alters ethanol sensitivity in a sexually dimorphic manner, since neuronal activation enhanced ethanol sedation in males, but not females. Finally, we provide anatomical evidence that tank-expressing neurons form likely synaptic connections with neurons expressing the neural sex determination factor fruitless (fru), which have been implicated recently in the regulation of ethanol sensitivity. We suggest that a functional interaction with fru neurons, many of which are sexually dimorphic, may account for the sex-specific effect induced by activating tank neurons. Overall, we have characterized a novel gene and corresponding set of neurons that regulate ethanol sensitivity in Drosophila.

Chronic tolerance to ethanol-induced sedation: Implication for age-related differences in locomotor sensitization

The adolescent brain has been suggested to be particularly sensitive to ethanol-induced neuroadaptations, which in turn could increase the risk of youths for alcohol abuse and dependence. Sensitization to the locomotor stimulant effects of ethanol has often been used as an animal model of ethanol-induced neuroadaptations. Previously, we showed that young mice were more sensitive than adults to the locomotor sensitization induced by high ethanol doses. However, this effect could be due to age-related differences in chronic tolerance to the sedative effects of ethanol. The aim of the present study is to assess chronic tolerance to the sedative effects of ethanol in weaning 21-day-old (P21), adolescent 35-day-old (P35) and adult 63-day-old (P63) female Swiss mice. After a daily injection of saline or 4 g/kg ethanol during 6 consecutive days, all P21, P35 and P63 mice were injected with 4 g/kg ethanol and submitted to the loss of righting reflex procedure. Our results confirm that the sensitivity to the acute sedative effects of ethanol gradually increases with age. Although this schedule of ethanol injections induces significant age-related differences in ethanol sensitization, it did not reveal significant differences between P21, P35 and P63 mice in the development of a chronic ethanol tolerance to its sedative effects. The present results show that age-related differences in the development of ethanol sensitization cannot be explained by differences in chronic ethanol tolerance to its sedative effects. More broadly, they do not support the idea that ethanol-induced sensitization is a by-product of chronic ethanol tolerance.

Histological studies on the hazardous effects of ethanol on liver and sple en in Swiss albino mice

Considering that ethanol caused number of health problems in the world, the present study was initiated to investigate the histological hazardous effects of ethanol on the liver and spleen. Animals were divided into 4 groups, the first group served as a control group, the second, third and fourth received 1,2 and 6 ml/kg/bw of 70% ethanol respectively. At the day 5 post treatment, the liver and spleen sections were prepared for the histological study. Ethanol intake induced marked histologyical alterations in the liver and spleen that correlated with the dose taken, low dose induced liver and spleen injury mainly as cytoplasmic degeneration in liver and abnormal structure of spleen, whereas, high doses of ethanol resulted in fibrosis in liver and splenomegaly.

A Small Group of Neurosecretory Cells Expressing the Transcriptional Regulatoraponticand the NeuropeptidecorazoninMediate Ethanol Sedation in Drosophila

In the fruit fly Drosophila melanogaster, as in mammals, acute exposure to a high dose of ethanol leads to stereotypical behavioral changes beginning with increased activity, followed by incoordination, loss of postural control, and eventually, sedation. The mechanism(s) by which ethanol impacts the CNS leading to ethanol-induced sedation and the genes required for normal sedation sensitivity remain largely unknown. Here we identify the gene apontic (apt), an Myb/SANT-containing transcription factor that is required in the nervous system for normal sensitivity to ethanol sedation. Using genetic and behavioral analyses, we show that apt mediates sensitivity to ethanol sedation by acting in a small set of neurons that express Corazonin (Crz), a neuropeptide likely involved in the physiological response to stress. The activity of Crz neurons regulates the behavioral response to ethanol, as silencing and activating these neurons affects sedation sensitivity in opposite ways. Furthermore, this effect is mediated by Crz, as flies with reduced crz expression show reduced sensitivity to ethanol sedation. Finally, we find that both apt and crz are rapidly upregulated by acute ethanol exposure. Thus, we have identified two genes and a small set of peptidergic neurons that regulate sensitivity to ethanol-induced sedation. We propose that Apt regulates the activity of Crz neurons and/or release of the neuropeptide during ethanol exposure.

Inhibition of Rat Muscle and Liver Phosphofructokinases by High Doses of Ethanol

Activities of both rat muscle and liver phosphofructokinases are significantly inhibited after a single ethanol intake in the dose of 2.5 g per kg of body weight. This inhibitory effect is indirect, since ethanol in concentration (50 mM) close to that established after 2.5 g per kg of body weight intake cannot decrease their activities in vitro. Inhibition of liver phosphofructokinase activity after the 5.0 g per kg ethanol intake may be direct, since liver phosphofructokinase activity decreases in vitro when ethanol is added to supernatants of rat liver tissue in 100 mM concentration. According to the results of molecular docking, ethanol at high concentrations can be bound by adenine-binding pocket of the allosteric ADP-binding site of liver phosphofructokinase (Asp543, Phe308, Phe538, and Phe671) and its activation by ADP can be blocked by C2H5OH molecule. Direct inhibition of muscle phosphofructokinase activity, probably due to the binding of ethanol to the similar ADP-binding site, is possible when the concentration of ethanol (500 mM) is much higher than the level which can be established in living cells. So, inhibition of muscle phosphofructokinase activity after a single 5.0 g per kg intake is indirect and probably linked with the inhibition of the enzyme by elevated citrate and phosphoenolpyruvate levels.

Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates

Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4–9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure.

Evaluation of the neurotoxic effects of ethanol on the cerebellar and cortical neurospheres isolated from E14 mouse embryo

Objectives: Ethanol exposure during pregnancy has toxic effects on the neural stem cells of the developing brain. Differential effects of the alcohol on the neural precursor cells from different regions of the brain have not been established. This study was planned to find out the difference in the morphology of the neurosphere (NS) from the embryonic mouse cortex and cerebellum when exposed to ethanol. The dose of ethanol was comparable to blood alcohol concentration in binge drinking. Materials and methods: The germinal tissues around the lateral ventricle and fourth ventricle of the embryo of pregnant albino mice (E14) were dissected out. Primary cultures were plated using adequate density of cells in media hormone mix (MHM) and growth factors. After 48 hours, ethanol was added to the cultures (low dose = 80 mg/dl; high dose = 400 mg/dl). NS from different groups were analyzed using phase-contrast microscopy, Trypan blue exclusion assay and immunostaining with 4'-6-Diamidino-2-phenylindol (DAPI). Results: With low dose ethanol treatment, the mean area of cortical neurospheres was reduced by 6.9% whereas that of the cerebellar neurospheres was reduced by 51.2%. The mean count of pyknotic cells increased significantly (p<0.05) in both low and high dose ethanol treatment group compared to control in both cortical and cerebellar culture. Cerebellar culture showed 4-fold-increase in mean pyknotic cells compared to 2.5-fold-increase in cortical culture, when exposed to ethanol. Conclusions: Cerebellar neural precursor cells from E14 mouse were more susceptible to the neurotoxic effects of ethanol compared to the cortical ones.

The dorsal striatum expressing adenylyl cyclase-5 controls behavioral sensitivity of the righting reflex to high-dose ethanol

High-dose ethanol inflicts sedation and loss of righting reflex (LORR). Recently, it was reported that AC5 knockout (AC5−/−) mice consumed more ethanol and showed reduced sensitivity to high-dose ethanol compared to wild-type mice. As an extension of the previous study, in the present study we examined the signaling mechanism regulating altered behavioral sensitivity of LORR in AC5−/− mice. AC5−/− mice had enhanced phosphorylation of the NR2B subunit of NMDA receptors in the dorsal striatum and a partial reduction of MK801 (NMDA receptor antagonist)/ethanol-induced LORR. AC5−/− mice showed increased levels of phospho-CaMKIIα, phospho-CREB, and BDNF in the dorsal striatum. CaMKIIα+/− or BDNF+/− mice displayed enhanced LORR, a behavioral phenotype opposite to that displayed by AC5−/− mice. Consistently with these results, stereotaxic infusion of KN62 (CaMKII inhibitor), siRNA-CaMKIIα, or siRNA-BDNF, within the dorsal striatum was sufficient to prolong LORR. These results suggest that neural mechanism is important for regulating behavioral sensitivity of LORR and that the signaling pathway(s) interplayed by AC5, CaMKIIα and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR.

Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed.

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: Possible mechanism for offspring ethanol overconsumption

Exposure to ethanol during the prenatal period contributes to increased alcohol consumption and preference in rodents and increased risk for alcoholism in humans. With studies in adult animals showing the orexigenic peptides, enkephalin (ENK), galanin (GAL) and orexin (OX), to stimulate ethanol consumption, the question addressed here is whether prenatal ethanol alters the development in utero of specific neurons that express these peptides. With reports describing suppressive effects of high doses of ethanol, we examined the offspring of dams gavaged from embryonic day 9 to parturition with a control solution or lower ethanol doses, 1 and 3g/kg/day, known to promote ethanol consumption in the offspring. To understand underlying mechanisms, measurements were taken in postnatal offspring of the expression of ENK in the hypothalamic paraventricular nucleus (PVN) and nucleus accumbens (NAc), GAL in the PVN, and OX in the perifornical lateral hypothalamus (PFLH) using real-time qPCR and in situ hybridization, and also of the cell proliferation marker, 5-bromo-2-deoxyuridine (BrdU), and its double-labeling with either neuronal nuclei (NeuN), a marker of mature neurons, or the peptides. On postnatal day 15 (P15), after two weeks without ethanol, the offspring showed increased expression of ENK in the PVN and NAc core but not shell, GAL in the PVN, and OX in the PFLH. In these same areas, prenatal ethanol compared to control increased the density at birth (P0) of neurons expressing these peptides and at P0 and P15 of neurons double-labeling BrdU and NeuN, indicating increased neurogenesis. These BrdU-positive neurons were found to express ENK, GAL and OX, indicating that prenatal ethanol promotes neurogenesis in these specific peptide systems. There were no changes in gliogenesis or apoptosis. This increase in neurogenesis and density of peptide-expressing neurons suggests the involvement of these hypothalamic and accumbal peptide systems in mediating the increased alcohol consumption observed in prenatal ethanol-exposed offspring.

Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover

Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I–III the less affected by the hangover condition; complex II–III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.