• Energy Research
• Restricted close
• Open Source close
• CN close
• RU close
• SE close
• Neuroscience close

Studies have shown that alcohol could impair automatic pre-attentive change detection. However, several earlier studies which investigated alcohol-induced effects on single auditory feature independently were different from each other on the results. Meanwhile, only few auditory features have been investigated yet. Therefore, it is meaningful to investigate effects of alcohol on multiple auditory features in one experiment.This study investigates the effects of alcohol on automatic pre-attentive change detection of four kinds of auditory features (frequency, intensity, location, and duration) in one experiment.This study, using multi-feature oddball paradigm, compares and analyzes mismatch negativity (MMN) elicited by four kinds of auditory features (frequency, intensity, location, and duration), of 12 participants, under alcohol (0.65 g/kg) and non-alcohol condition.Compared to non-alcohol condition, amplitudes of all the four MMN types significantly declined under alcohol condition, and their amplitude decline ratios decreased as deviant magnitude became larger. Latencies of frequency and intensity MMN were delayed while latencies of location and duration MMN were not delayed significantly.Alcohol impaired automatic pre-attentive change detection of all the four auditory features (frequency, intensity, location, and duration). However, the alcohol-induced impairment magnitude on automatic pre-attentive detection of the four auditory features was different from each other. According to analysis of amplitude, frequency seems to be affected most among the four auditory features. According to analysis of latency, only frequency and intensity were affected.

Animal models have suggested that prenatal ethanol exposure (PEE) alters the κ opioid receptor system. The present study investigated the brain expression of dynorphin and nociceptin/orphanin FQ related genes and assessed anxiety-like behavior in the light-dark box (LDB), shelter-seeking and risk-taking behaviors in the concentric square field (CSF) test, and ethanol-induced locomotion in the open field (OF), in infant or adolescent Wistar rats that were exposed to PEE (0.0 or 2.0 g/kg, intragastrically, gestational days 17-20). We measured brain mRNA levels of prodynorphin (PDYN), κ opioid receptors (KOR), the nociceptin/orphanin FQ opioid peptide precursor prepronociceptin (ppN/OFQ) and nociceptine/orphanin FQ receptors (NOR). Prenatal ethanol exposure upregulated PDYN and KOR mRNA levels in the ventral tegmental area (VTA) in infant and adolescent rats and KOR mRNA levels in the prefrontal cortex in infant rats. The changes in gene expression in the VTA were accompanied by a reduction of DNA methylation at the PDYN gene promoter, and by a reduction of DNA methylation at the KOR gene promoter. The PEE-induced upregulation of PDYN/KOR in the VTA was accompanied by lower NOR gene expression in the VTA, and lower PDYN gene expression in the nucleus accumbens. PEE rats exhibited hypolocomotion in the OF, greater avoidance of the white and brightly lit areas in the LDB and CSF, and greater preference for the sheltered area in the CSF test. These results suggest that PEE upregulates the dynorphin system, resulting in an anxiety-prone phenotype and triggering compensatory responses in the nociceptin/orphanin FQ system. These findings may help elucidate the mechanisms that underlie the effects of PEE and suggest that the dynorphin and nociceptin/orphanin FQ systems may be possible targets for the prevention and treatment of PEE-induced alterations.

Serotonin (5-HT) plays an important role in the organization of the central nervous system and in the development of social interaction deficits and psychiatric disorders, including anxiety, depression, and addiction disorders. Notably, disruption of the 5-HT system during sensitive periods of development exerts long-term consequences, including altered anxiety response and problematic use of alcohol.we analyzed, in mice, the effects of transient 5-HT depletion at infancy or adolescence on subsequent anxiety-like behavior and alcohol intake during adolescence.C57/BL6 male and female mice were administered a 5-HT synthesis inhibitor (PCPA; 4-chloro-DL-phenylalanine methyl ester hydrochloride) at infancy (postnatal days 14-16 [PD14-16]) or adolescence (PD40-42). Eleven (± 1) days after treatment, mice were assessed for ethanol intake in daily two-bottle choice tests and for anxiety response via the elevated plus maze.Female, but not male, mice transiently depleted of 5-HT at adolescence (but not those depleted at the perinatal stage) exhibited a significant reduction in anxiety response, which was accompanied by a significant reduction on alcohol intake.Transient 5-HT inhibition at adolescence may act, in females, as a protective factor for the emergence of anxiety disorders and problematic use of alcohol during adolescence.

Repeated treatment of rats with ethanol (1 g/kg, once daily for 15 days) enhanced the locomotor effect of morphine, 3 weeks post-treatment. This ethanol-induced long-term behavioural sensitization to morphine was associated with an increase in the electrically evoked release of [3H]dopamine (DA) and [14C]acetylcholine (ACh) from nucleus accumbens slices. A similar enhanced responsiveness of accumbal dopaminergic and cholinergic neurons to depolarization was apparent 3 weeks after repeated morphine, amphetamine or cocaine administration. Prior ethanol exposure also caused a long-term enhancement of electrically evoked release of [3H]DA and [14C]ACh from slices of the caudate-putamen. Unlike the locomotor effect of morphine, that of amphetamine was not enhanced in ethanol-pretreated rats. These data indicate that ethanol administration may cause long-term behavioural sensitization associated with adaptive changes in dopaminergic and cholinergic neurons of rat nucleus accumbens and caudate-putamen. Furthermore, an enhanced reactivity of nucleus accumbens dopaminergic nerve terminals and dopamine-sensitive cholinergic neurons appears to be a common long-term neuroadaptive effect of distinct types of addictive drugs. However, since repeated ethanol exposure did not cause a long-term increase in the locomotor effect of amphetamine, these neuroadaptations may not always be sufficient to cause long-lasting behavioural (cross-)sensitization.

Background: Fetal alcohol spectrum disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with fetal alcohol syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. Hypothesis/Objective: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF- α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

In the present study, the reactivity of striatal dopamine and dopamine-sensitive neurons in super-fused striatal slices of ethanol-experienced rats was compared to that of ethanol-naive rats, 3 weeks after oral ethanol self-administration. During the acquisition phase (17 days), rats were offered increasing concentrations of ethanol (from 2 to 10%, 24 h per day) on an alternate-day schedule in a free choice with water. Following 2 weeks of unrestricted 10% ethanol consumption, the highest and lowest drinkers (representing about 25% of the upper and lower extremes of the total population) were selected. Preliminary experiments revealed that both groups of rats displayed a profound increase in ethanol consumption and preference 3 weeks after cessation of ethanol self-administration (deprivation effect). This deprivation effect was associated with an increase in electrically evoked release of [3H]dopamine from superfused nucleus accumbens slices, whereas the evoked [3H]dopamine release from caudate putamen slices remained unchanged. In slices of the caudate putamen, but not in nucleus accumbens slices, postsynaptic dopamine D1 receptor-stimulated cyclic AMP production was also enhanced. In addition, prior ethanol consumption enhanced the electrically evoked release of [14C]acetylcholine release in both striatal regions. Interestingly, the magnitude of these long-term neuroadaptations correlated with the amount of daily ethanol consumption, i.e. neuronal hyperresponsiveness in the striatum was more profound in the high than in the low ethanol drinkers. These data show for the first time that unrestricted free-choice ethanol consumption in rats is associated with a long-term increase in dopaminergic and cholinergic neurotransmission in the nucleus accumbens and caudate putamen. These (and other) neuroadaptations may underlie the enhanced motivation to self-administer ethanol and the maintenance of ethanol consumption long after deprivation.

Ethanol exposure during gestation is an early life stressor that profoundly dysregulates structure and functions of the embryonal nervous system, altering the cognitive and behavioral development. Such dysregulation is also achieved by epigenetic mechanisms, which, altering the chromatin structure, redraw the entire pattern of gene expression. In parallel, an oxidative stress response at the cellular level and a global upregulation of neuroendocrine stress response, regulated by the HPA axis, exist and persist in adulthood. This neurobehavioral framework matches those observed in other psychiatric diseases such as mood diseases, depression, autism; those early life stressing events, although probably triggered by specific and different epigenetic mechanisms, give rise to largely overlapping neurobehavioral phenotypes. An early diagnosis of prenatal alcohol exposure, using reliable markers of ethanol intake, together with a deeper understanding of the pathogenic mechanisms, some of them reversible by their nature, can offer a temporal "window" of intervention. Supplementing a mother's diet with protective and antioxidant substances in addition to supportive psychological therapies can protect newborns from being affected.