Piecing together the puzzle of acetaldehyde as a neuroactive agent |
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| Authors: | Correa Mercè Salamone John D Segovia Kristen N Pardo Marta Longoni Rosanna Spina Liliana Peana Alessandra T Vinci Stefania Acquas Elio |
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| Affiliation: | a Department of Psychobiology, University Jaume I, 12071 Castelló, Spain
b Department of Behavioral Neuroscience, University of Connecticut, 06269-1020, Storrs, USA
c Department of Toxicology, University of Cagliari, Italy
d INN - National Institute of Neuroscience, University of Cagliari, Italy
e Department of Drug Sciences, University of Sassari, Italy
f Centre of Excellence on Neurobiology of Addiction, University of Cagliari, I-09124 Cagliari, Italy |
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| Abstract: | Mainly known for its more famous parent compound, ethanol, acetaldehyde was first studied in the 1940s, but then research interest in this compound waned. However, in the last two decades, research on acetaldehyde has seen a revitalized and uninterrupted interest. Acetaldehyde, per se, and as a product of ethanol metabolism, is responsible for many pharmacological effects which are not clearly distinguishable from those of its parent compound, ethanol. Consequently, the most recent advances in acetaldehyde's psychopharmacology have been inspired by the experimental approach to test the hypothesis that some of the effects of ethanol are mediated by acetaldehyde and, in this regard, the characterization of metabolic pathways for ethanol and the localization within discrete brain regions of these effects have revitalized the interest on the role of acetaldehyde in ethanol's central effects. Here we present and discuss a wealth of experimental evidence that converges to suggest that acetaldehyde is an intrinsically active compound, is metabolically generated in the brain and, finally, mediates many of the psychopharmacological properties of ethanol. |
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| Keywords: | 4MP, 4-methylpyrazole AA, Alko alcohol Acb, nucleus accumbens AcbSh, nucleus accumbens shell AcbC, nucleus accumbens core aCSF, artificial cerebrospinal fluid ADH, alcohol dehydrogenase ALDH, aldehyde dehydrogenase ANA, alko non-alcohol ANT, alcohol sensitive rats ARH, arcuate nucleus of the hypothalamus ASOs, antisense phosphorothioate oligonucleotides AT, alcohol-resistant ATZ, aminotriazole BAAC, blood acetaldehyde concentration BBB, blood brain barrier BEC, blood ethanol concentration BSTL, bed nucleus of the stria terminalis CeA, central nucleus of the amygdala CPA, conditioned place avoidance CPP, conditioned place preference CTA, conditioned taste aversion CTP, conditioned taste preference CYP, cytochrome P450 DA, dopamine DMS, dorsomedial striatum DDTC, diethyl dithiocarbamate DOPAL, dihydroxyphenylacetaldehyde DOPAC, dihydroxyphenylacetic acid DRL, differential-reinforcement-of-low-rates-of-responding ER, exploration ratio ERK, extracellular signal regulated kinase HAP, high alcohol-preference rats FR, fixed ratio HPV, paraventricular nucleus of the hypothalamus IA, A-type potassium current Ih, hyperpolarization-activated inward potassium current i.c., intracisternal administration i.c.v., intracerebroventricular administration i.g., intragastric administration i.p., intraperitoneal administration IRT, inter-response time i.v., intravenous administration KO, knock out LAP, low alcohol-preference rats MAPK, mitogen activated protein kinases MEK, mitogen-activating ERK kinase NTS, nucleus of the solitary tract P, Alcohol preferring rats PBN, parabrachial nucleus SC, superior colliculus SNc, substantia nigra, pars compacta SNr, substantia nigra, pars reticulata THP, tetrahydropapaveroline ThPV/PF, paraventricular/parafascicular nuclei of thalamus TR, taste reactivity UChA, University of Chile high alcohol drinkers UChB, University of Chile low alcohol drinkers VLS, ventrolateral striatum VP, ventral pallidum VTA, ventral tegmental area WT, wild type |
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