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Association studies implicate multiple PDZ domain protein (MPDZ/MUPP1) sequence and/or expression in risk for alcoholism in humans and ethanol withdrawal (EW) in mice, but confirmation has been hindered by the dearth of targeted genetic models. We report the creation of transgenic (MPDZ-TG) and knockout heterozygote (Mpdz(+/-) ) mice, with increased (2.9-fold) and decreased (53%) target expression, respectively. Both models differ in EW compared with wild-type littermates (P ≤ 0.03), providing compelling evidence for an inverse relationship between Mpdz expression and EW severity. Additionally, ethanol consumption is reduced up to 18% (P = 0.006) in Mpdz(+/-) , providing the first evidence implicating Mpdz in ethanol self-administration.
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http://dx.doi.org/10.1111/adb.12087 | DOI Listing |
Cureus
July 2025
Internal Medicine, BronxCare Health System, Bronx, USA.
Acute pancreatitis, a common cause of acute abdomen, is known to have a broad spectrum of local and systemic complications. Vascular complications of acute pancreatitis are vastly underreported. Our case, a 66-year-old male patient with alcohol-induced acute pancreatitis and concurrent severe ethanol withdrawal syndrome, who developed extensive thrombotic events early in the disease course, is a rare and intriguing presentation.
View Article and Find Full Text PDFFront Pharmacol
August 2025
Faculty of Health Sciences, Institute of Biomedical Sciences, Universidad Autónoma de Chile, Santiago, Chile.
Alcohol use disorder (AUD) and major depression frequently co-occur, both involving significant neuroinflammatory components. Current treatments are often ineffective in addressing AUD-related depression, highlighting the need for novel therapeutic approaches. Previous studies showed that fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, reduces voluntary alcohol intake and attenuates neuroinflammation and oxidative stress in alcohol-preferring rats.
View Article and Find Full Text PDFNeuropharmacology
November 2025
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, United States. Electronic address:
Relapse remains a major challenge in the treatment of alcohol use disorder, driven in part by persistent neuroadaptations. However, how different post-alcohol experiences, such as passive withdrawal (abstinence) versus active extinction training, differentially shape the neural circuits and synaptic mechanisms that influence relapse vulnerability remains unclear. Here, we show that these experiences have opposing effects on dorsomedial striatal (DMS) direct-pathway medium spiny neurons (dMSNs) and dopamine dynamics during cue-induced reinstatement of alcohol seeking.
View Article and Find Full Text PDFAlcohol Clin Exp Res (Hoboken)
August 2025
Department of Psychobiology and Behavioral Sciences Methods, Faculty of Psychology, Complutense University of Madrid, Madrid, Spain.
Background: Memory impairment is frequent among alcohol use disorder (AUD) patients, and we lack specific biomarkers to detect it. Certain apolipoproteins were linked to cognition, and carrying the APOE4 gene is a vulnerability factor to memory impairment in AUD patients. We explored memory deficits in alcohol-dependent male mice and humans versus controls, and their relationship to Apolipoprotein AI (APOAI), apolipoprotein B (APOB), and apolipoprotein E (APOE) plasma levels.
View Article and Find Full Text PDFInt J Neuropsychopharmacol
August 2025
IUNICS, University of the Balearic Islands, Palma, Spain.
Background: Ethanol use is frequently initiated during adolescence, a vulnerable developmental period with a great deal of neuro-remodeling, specially affecting hippocampal integrity, and with a unique sensitivity to drug abuse. Previous data evaluated the neurochemical effects exerted by either ethanol or cocaine alone in the adolescent brain, but few studies measured the combined negative impact of both drugs immediate during adolescence and later following withdrawal and drug re-exposure in adulthood and therefore will be the aim of this study.
Methods: Male and female Sprague-Dawley rats were treated in adolescence with non-contingent paradigms of ethanol, cocaine, their combination or vehicle.