Alcoholism, clinical and experimental research
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Alcohol. Clin. Exp. Res. · Mar 2014
Differential role of D1 and D2 receptors in the perifornical lateral hypothalamus in controlling ethanol drinking and food intake: possible interaction with local orexin neurons.
The neurotransmitter dopamine (DA), acting in various mesolimbic brain regions, is well known for its role in promoting motivated behaviors, including ethanol (EtOH) drinking. Indirect evidence, however, suggests that DA in the perifornical lateral hypothalamus (PF/LH) has differential effects on EtOH consumption, depending on whether it acts on the DA 1 (D1) or DA 2 (D2) receptor subtype, and that these effects are mediated in part by local peptide systems, such as orexin/hypocretin (OX) and melanin-concentrating hormone (MCH), known to stimulate the consumption of EtOH. ⋯ These results support a stimulatory role of the PF/LH D1 receptor in promoting the consumption of both EtOH and food, in contrast to a suppressive effect of the D2 receptor on EtOH drinking. They further suggest that these receptors affect consumption, in part, through local OX-expressing neurons. These findings provide new evidence for the function of PF/LH DA receptor subtypes in controlling EtOH and food intake.
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Alcohol. Clin. Exp. Res. · Feb 2014
Activation of the epithelial-to-mesenchymal transition factor snail mediates acetaldehyde-induced intestinal epithelial barrier disruption.
Acetaldehyde (AcH) is mutagenic and can reach high concentrations in colonic lumen after ethanol consumption and is associated with intestinal barrier dysfunction and an increased risk of progressive cancers, including colorectal carcinoma. Snail, the transcription factor of epithelial-mesenchymal transition, is known to down-regulate expression of tight junction (TJ) and adherens junction (AJ) proteins, resulting in loss of epithelial integrity, cancer progression, and metastases. As AcH is mutagenic, the role of Snail in the AcH-induced disruption of intestinal epithelial TJs deserves further investigation. Our aim was to investigate the role of oxidative stress and Snail activation in AcH-induced barrier disruption in Caco-2 monolayers. ⋯ Our data demonstrate that oxidative stress-mediated Snail phosphorylation is likely a novel mechanism contributing to the deleterious effects of AcH on the TJ and AJ, and intestinal barrier function.
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Alcohol. Clin. Exp. Res. · Feb 2014
Prenatal alcohol exposure is associated with altered subcellular distribution of glucocorticoid and mineralocorticoid receptors in the adolescent mouse hippocampal formation.
Accumulating evidence indicates that several of the long-term consequences of prenatal alcohol exposure (PAE) are the result of changes in the development and function of cortico-limbic structures, including the hippocampal formation. The glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are key regulators of hippocampal formation development, structure, and functioning and, thus, are potential mediators of PAE's effects on this brain region. In the present studies, we assessed the impact of PAE on components of corticosteroid signaling pathways in the mouse hippocampal formation. ⋯ The data support a model in which PAE leads to increased nuclear localization of GRs secondary to reductions in FKBP51 and increases in 11β-HSD1 levels in the adolescent mouse hippocampal formation. Persistent dysregulation of GR subcellular distribution is predicted to damage the hippocampal formation and may underlie many of the effects of PAE on hippocampal-dependent functioning.
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Alcohol. Clin. Exp. Res. · Jan 2014
Initial evidence that OPRM1 genotype moderates ventral and dorsal striatum functional connectivity during alcohol cues.
Endogenous opioids and striatal dopamine have been implicated in cue-induced alcohol craving and have been hypothesized to play a role in goal-directed, as opposed to habitual, alcohol use. This initial study examines dorsal and ventral striatal functional connectivity during alcohol-cue processing as a function of the A118G single-nucleotide polymorphism of the mu-opioid receptor (OPRM1) gene. ⋯ These preliminary findings suggest that, relative to A-allele homozygotes, G-allele carriers show unstable frontal regulation over reward and/or habit-driven inputs from the striatum resulting from greater reward sensitivity combined with limited self-control resources.
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Alcohol. Clin. Exp. Res. · Jan 2014
Multicenter StudyThe Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) in the assessment of alcohol use disorders among acute injury patients.
The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is a brief alcohol screening test and a candidate for inclusion in recommended screening and brief intervention protocols for acute injury patients. The objective of the current study was to examine the performance of the AUDIT-C to risk stratify injury patients with regard to their probability of having an alcohol use disorder. ⋯ The findings of SSLR analysis can be used to improve estimates of the probability of alcohol use disorder in acute injury patients based on AUDIT-C scores. In turn, this information can inform clinical interventions and the development of screening and intervention protocols in a range of settings.