ACETALDEHYDE EFFECTS IN THE BRAIN FULVIO PLESCIA 1 , EMANUELE CANNIZZARO 1 , ANNA BRANCATO 1,2 , FRANCESCO MARTINES 2 , ANGELO DI NARO , MARIANNA MUCIA 3 , FABIANA PLESCIA 4 , CARLOTTA VITA 1 , PIETRO SALVAGO 2, ANTONINO MULÈ 3 , SERENA RIZZO 2 , FEDERICO SIRECI 2 , CARLA CANNIZZARO 1 1 University of Palermo, Palermo, Department of Sciences for Health Promotion and Mother and Child Care “Giuseppe D'Alessandro”, Palermo - 2 University of Palermo, BioNeC Department, ENT Section, Palermo - 3 University of Palermo, Di.Bi.Me.F, Department, Audiology Section, Palermo - 4 University of Palermo, STEBICEF Department, Palermo, Italy Introduction Alcohol use disorder is considered a chronic relapsing and remitting disease defined by the development of tolerance, abstinence, drug con- sumption for alleviating abstinence, exaggerated consumption beyond original intention, failure to reduce drug consumption, use of a considerable amount of time to obtaining or recovering from the substance’s effects, and maintenance of drug con- sumption, despite facing adverse consequences (1,2) . In particular ethanol (EtOH) produces a wide range of neurocognitive effects such us impairment in judgment, learning, memory, perception and psy- chomotor agitation (3,4,5) . There is a growing body of evidence indicat- ing that acetaldehyde (ACD), the first oxidation product of ethanol, is one of the mediators of the peripheral and central effects of ethanol (6-14) . ACD is usually considered a highly aversive substance: in the past the indirect use of ACD was taken into account for discouraging drinking in alcoholic patients. In fact, several drugs able to inhibit the activity of aldehyde dehydrogenase (ALDH) such us disulfiram and calcium carbimide, were widely used in the treatment of withdrawn alcoholics to produce an aversion for alcohol (14) . Nevertheless, it was reported that patients under treatment with ALDH inhibitor declared pleasant relaxing effects, after taking small doses of ethanol, highlighting Acta Medica Mediterranea, 2015, 31: 813 Received November 30, 2014; Accepted May 02, 2015 ABSTRACT The effects of alcohol have been widely studied during the past century as alcohol abuse is a major health problem in Western society. In the last years, a growing body of evidence indicates that acetaldehyde, the first oxidation product of ethanol, is one of the mediators of peripheral and central effects of ethanol. Indeed, acetaldehyde has been recently taken into account as the mediator of the rewarding properties of alcohol. The role of acetaldehyde in ethanol-related properties has been proved by enzymatic manipula- tion studies in which the inactivation of acetaldehyde potentially synthesized in the brain produces the same results as blocking the formation of acetaldehyde by inhibiting brain catalase activity. Moreover, electrophysiological and pharmacological analyses showed that acetaldehyde is able to stimulate dopamine release in the nucleus accumbens through enhancement of firing rate, spikes/burst, and burst firing of ventral tegmental neurons. Thus, the aim of this review is to summarize latest results on the role of acetaldehyde as the mediator of ethanol-central effects. Key words: Acetaldehyde, Alcoholism, Ethanol-related effects, Dopaminergic pathway.