title: Acetaldehyde self-administration by a two-bottle choice paradigm: consequences on emotional reactivity, spatial learning, and memory.
abstract: Acetaldehyde, the first alcohol metabolite, is responsible for many pharmacological effects that are not clearly distinguishable from those exerted by its parent compound. It alters motor performance, induces reinforced learning and motivated behavior, and produces different reactions according to the route of administration and the relative accumulation in the brain or in the periphery. The effective activity of oral acetaldehyde represents an unresolved field of inquiry that deserves further investigation. Thus, this study explores the acquisition and maintenance of acetaldehyde drinking behavior in adult male rats, employing a two-bottle choice paradigm for water and acetaldehyde solution (from 0.9% to 3.2% v/v), over 8 weeks. The behavioral consequences exerted by chronic acetaldehyde intake are assessed by a set of different tests: trials in an open-field arena and elevated-plus maze provided information on both general motor and explorative activity, and anxiety-driven behavioral responses. The Morris water maze allowed the exploration of cognitive processes such as spatial learning and memory. Determination of acetaldehyde levels in the brain was carried out at the end of the drinking paradigm. Our results indicate that rats exposed for the first time to acetaldehyde at 0.9% displayed a regular and stable daily drinking pattern that reached higher values and a "peaks and drops" shaped-trend when acetaldehyde concentration was increased to 3.2%. Accordingly, an increase in acetaldehyde levels in the brain was determined compared to non-acetaldehyde drinking rats. Acetaldehyde intake during the free-choice paradigm exerted an anxiogenic response in the open-field arena and elevated-plus maze, which in turn correlates with an enhancement in cognitive flexibility and spatial orientation skills, when an adaptive response to a stressful environmental challenge was required. These findings further support the idea that acetaldehyde is indeed a centrally active and behaviorally relevant metabolite of alcohol.
authors: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy.
authors: Fulvio
authors: F
authors: Plescia
authors: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy; BioNeC, University of Palermo, 90134 Palermo, Italy.
authors: Anna
authors: A
authors: Brancato
authors: Department of Public Health and Community Medicine, Section of Pharmacology, University of Verona, Policlinico G. B. Rossi, Piazzale Scuro 10, 36134 Verona, Italy.
authors: Marco
authors: M
authors: Venniro
authors: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy; BioNeC, University of Palermo, 90134 Palermo, Italy.
authors: Giuseppe
authors: G
authors: Maniaci
authors: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy.
authors: Emanuele
authors: E
authors: Cannizzaro
authors: STEBICEF, University of Palermo, 90123 Palermo, Italy; BioNeC, University of Palermo, 90134 Palermo, Italy.
authors: Flavia Maria
authors: FM
authors: Sutera
authors: STEBICEF, University of Palermo, 90123 Palermo, Italy.
authors: Viviana
authors: V
authors: De Caro
authors: STEBICEF, University of Palermo, 90123 Palermo, Italy.
authors: Libero Italo
authors: LI
authors: Giannola
authors: Department of Sciences for Health Promotion and Mother and Child Care "Giuseppe D'Alessandro", University of Palermo, Via del Vespro 133, 90127 Palermo, Italy. Electronic address: carla.cannizzaro@unipa.it.
authors: Carla
authors: C
authors: Cannizzaro
mesh_terms: D000079:Acetaldehyde / Q000008:administration & dosage* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002755:Choice Behavior / Q000187:drug effects* / Q000502:physiology; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D065853:Spatial Learning / Q000187:drug effects* / Q000502:physiology
chemical_list: D000079:Acetaldehyde
keywords: Acetaldehyde in the brain; Anxiety-like behavior; Emotional reactivity; Spatial learning and memory; Two-bottle choice paradigm