title: Centrally formed acetaldehyde mediates ethanol-induced brain PKA activation.
abstract: Centrally formed acetaldehyde has proven to be responsible for several psychopharmacological effects induced by ethanol. In addition, it has been suggested that the cAMP-PKA signaling transduction pathway plays an important role in the modulation of several ethanol-induced behaviors. Therefore, we hypothesized that acetaldehyde might be ultimately responsible for the activation of this intracellular pathway. We used three pharmacological agents that modify acetaldehyde activity (α-lipoic acid, aminotriazole, and d-penicillamine) to study the role of this metabolite on EtOH-induced PKA activation in mice. Our results show that the injection of α-lipoic acid, aminotriazole and d-penicillamine prior to acute EtOH administration effectively blocks the PKA-enhanced response to EtOH in the brain. These results strongly support the hypothesis of a selective release of acetaldehyde-dependent Ca(2+) as the mechanism involved in the neurobehavioral effects elicited by EtOH.
authors.affiliation: Área de Psicobiología, Universitat Jaume I, Castellon de la Plana, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Tarragon
authors.affiliation: Área de Psicobiología, Universitat Jaume I, Castellon de la Plana, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Baliño
authors.affiliation: Área de Psicobiología, Universitat Jaume I, Castellon de la Plana, Spain. Electronic address: aragon@psb.uji.es.
authors.forename: C M G
authors.initials: CM
authors.lastname: Aragon
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism*; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010396:Penicillamine / Q000494:pharmacology; D010766:Phosphorylation; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D000431:Ethanol; D008063:Thioctic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D010396:Penicillamine; D000079:Acetaldehyde; D000640:Amitrole
keywords: Acetaldehyde; Ethanol; PKA