• Energy Research
• 3. Good health close
• IT close
• ES close
• EU close
• Neuroscience close

In the present study, we aimed to assess the impact of early life stress, in the form of early maternal deprivation (MD, 24 h on postnatal day, pnd, 9), on voluntary alcohol intake in adolescent male and femaleWistarrats. During adolescence, from pnd 28 to pnd 50, voluntary ethanol intake (20%, v/v) was investigated using the two-bottle free choice paradigm. To better understand the relationship between stress and alcohol consumption, voluntary alcohol intake was also evaluated following additional stressful events later in life, that is, a week of alcohol cessation and a week of alcohol cessation combined with exposure to restraint stress. Female animals consumed more alcohol than males only after a second episode of alcohol cessation combined with restraint stress. MD did not affect baseline voluntary alcohol intake but increased voluntary alcohol intake after stress exposure, indicating that MD may render animals more vulnerable to the effects of stress on alcohol intake. During adolescence, when animals had free access to alcohol, MD animals showed lower body weight gain but a higher growth rate than control animals. Moreover, the higher growth rate was accompanied by a decrease in food intake, suggesting an altered metabolic regulation in MD animals that may interact with alcohol intake.

Human genetic variation in the nicotinic receptor gene cluster CHRNA5/A3/B4, in particular the non-synonymous and frequent CHRNA5 variant rs16969968 (α5SNP), has an important consequence on smoking behavior in humans. A number of genetic association studies have additionally implicated the CHRNA5 gene in addictions to other drugs, and also body mass index (BMI). Here, we model the α5SNP, in a transgenic rat line, and establish its role in alcohol dependence, and feeding behavior. Rats expressing the α5SNP consume more alcohol, and exhibit increased relapse to alcohol seeking after abstinence. This high-relapsing phenotype is reflected in altered activity in the insula, linked to interoception, as established using c-Fos immunostaining. Similarly, relapse to food seeking is increased in the transgenic group, while a nicotine treatment reduces relapse in both transgenic and control rats. These findings point to a general role of this human polymorphism in reward processing, and multiple addictions other than smoking. This could pave the way for the use of medication targeting the nicotinic receptor in the treatment of alcohol use and eating disorders, and comorbid conditions in smokers.

Recent electrophysiological evidence suggests that ethanol simultaneously exerts opposite effects on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) through two parallel mechanisms, one promoting and the other reducing the GABA release onto VTA DA neurons. Here we explore the possible behavioural implications of these findings by investigating the role displayed by acetaldehyde (the main metabolite of ethanol) and the non-metabolized fraction of ethanol in motor activity of rats. We analyse the appearance of motor activation or depression after intra-VTA administration of ethanol in rats subjected to different pharmacological pre-treatments designed to preferentially test either the effects of acetaldehyde or the non-metabolized ethanol. Motor activity was evaluated after intra-VTA administration of 35 nmol of ethanol, an apparently ineffective dose that does not modify the motor activity of animals. Pharmacological pre-treatments were used in order to either increase (cyanamide, 10 mg/kg, ip) or decrease (D-penicillamine, 50 mg/kg, ip and sodium azide, 7 mg/kg, ip) acetaldehyde levels in the VTA. Pre-treatments aimed to augment acetaldehyde, increased motor activity of rats. Otherwise, pre-treatments intended to decrease local acetaldehyde levels evoked significant reductions in motor activity that were prevented by the local blockade (bicuculline, 17.5 pmol) of the GABAA receptors. Our findings suggest that the brain-generated acetaldehyde is involved in the stimulant effects of ethanol, whereas the non-biotransformed fraction of ethanol, acting through the GABAA receptors, would account for the depressant effects. The present behavioural findings suggest that ethanol dually modulates the activity of DA neurons.

The aim of this study was to evaluate the efficacy and tolerability of the DHP Ca2+ antagonist nimodipine in human AWS and post-AWS. Ten hospitalized alcoholics of both sexes with a diagnosis of AWS according to the DSM-III criteria were treated for 3 weeks in monotherapy with nimodipine p.o. at flexible daily dosages. Evaluation of AWS symptoms was performed at baseline and after 3, 5, 7, 10, 14 and 21 days. A statistically significant improvement of AWS was seen at evaluation on day 3, particularly in neurovegetative and psychopathological symptoms, and lasted up to the end of the study. The treatment was well tolerated and no side effects were observed or reported. In this pilot, open study nimodipine proved effective in the treatment of mild-to-moderate AWS. If these data are confirmed in a double-blind study nimodipine could be a rational alternative to benzodiazepines in the treatment of AWS.

The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol‐related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms.

Ecstasy abuse commonly occurs in hot, overcrowded environments in combination with alcohol. Around 90% of ecstasy users take ethanol; over 70% of these users also often drink alcohol at hazardous levels.We wished to examine whether binge ethanol administration enhanced the long-lasting 5-HT neurotoxicity induced by 3,4-methylenedioxymethamphetamine (MDMA) in rats maintained at high ambient temperature and the role of acetaldehyde.Rats were treated with a 4-day ethanol regimen leading to plasma ethanol levels of around 450 mg/dl. On day 5, rats were placed at 30 degrees C and administered MDMA (5 mg/kg). Rectal temperature and hydroxyl radical formation were measured immediately before and up to 6 h after MDMA. 5-HT concentration and 5-HT transporter density were determined 7 days later. A group of rats received cyanamide (50 mg/kg) on days 1 and 3 of the 4-day-ethanol inhalation.In ethanol treated rats, MDMA produced a hyperthermic response similar to that observed in controls but enhanced the loss of 5-HT concentration and 5-HT transporter density in the hippocampus. Cyanamide elevated the plasma acetaldehyde concentration fivefold to sevenfold, reduced the MDMA-induced hyperthermia and increased the neuronal damage with neurotoxicity also appearing in the cortex. MDMA increased hydroxyl radical production in the hippocampus, the effect being more marked in rats pre-exposed to ethanol.Binge ethanol administration enhances the MDMA-induced long-term 5-HT neurotoxicity by a mechanism not related to changes in acute hyperthermia but probably involving hydroxyl radical formation. The magnitude of this effect is more pronounced after increasing plasma acetaldehyde levels by aldehyde dehydrogenase inhibition.

A significant number of human immunodeficiency virus type 1 (HIV-1)-infected patients are alcoholics. Either alcohol or HIV alone induces morphological and functional damage to the nervous system. HIV-1 Tat is a potent transcriptional activator of the viral promoter, with the ability to modulate a number of cellular regulatory circuits including apoptosis and to cause neuronal injury. To further evaluate the involvement of alcohol in neuronal injury, the authors examined the effect of ethanol on Tat-induced calcium responses in rat cerebral cortical neurons, using microfluorimetric calcium determination. HIV Tat protein (10 or 500 nM) elicited two types of calcium responses in cortical neurons: a fast-onset, short-lasting response and a slow-onset, sustained response. The responses were concentration-dependent and diminished in calcium-free saline. A short exposure to ethanol (50 mM) potentiated both types of calcium response, which was markedly decreased when the cells were pretreated with BAPTA-AM (20 microM). In addition, an increase in the neurotoxic effect of Tat, which was assessed by trypan blue exclusion assay, was observed. The result led the authors to conclude that alcohol exposure significantly potentiates Tat-induced calcium overload and neuronal death.