What is in that Drink: The Biological Actions of Ethanol, Acetaldehyde, and Salsolinol

Abstract

Alcohol abuse and alcoholism represent substantial problems that affect a large portion of individuals throughout the world. Extensive research continues to be conducted in an effort to identify the biological basis of the reinforcing properties of alcohol in order to develop effective pharmacotherapeutic and behavioral interventions. One theory that has developed within the alcohol field over the past 4 decades postulates that the reinforcing properties of alcohol are due to the action of the metabolites/products of alcohol within the central nervous system (CNS). The most extreme version of this theory suggests that the biologically active metabolites/products of alcohol, created from the breakdown from alcohol, are the ultimate source of the reinforcing properties of alcohol. The contrary theory proposes that the reinforcing properties of alcohol are mediated completely through the interaction of the ethanol molecule with several neurochemical systems within the CNS. While there are scientific findings that offer support for both of these stances, the reinforcing properties of alcohol are most likely generated through a complex series of peripheral and central effects of both alcohol and its metabolites. Nonetheless, the development of a greater understanding for how the metabolites/products of alcohol contribute to the reinforcing properties of alcohol is an important factor in the development of efficacious pharmacotherapies for alcohol abuse and alcoholism. This chapter is intended to provide a historical perspective of the role of acetaldehyde (the first metabolite of alcohol) in alcohol reinforcement as well as review the basic research literature on the effects of acetaldehyde (and acetaldehyde metabolites/products) within the CNS and how these function with regard to alcohol reward.

P2X4 Receptor Regulates Alcohol-Induced Responses in Microglia

“…Alcohol abuse and alcoholism represent substantial problems that affect a large portion of the general public 1 . Alcohol is known to cause structural and functional abnormalities to the brain 1-6 including the significant risk associated with chronic alcohol abuse, particularly disorders of the central nervous system (CNS) 7 .…”

“…Alcohol is known to cause structural and functional abnormalities to the brain 1-6 including the significant risk associated with chronic alcohol abuse, particularly disorders of the central nervous system (CNS) 7 . Alcohol is known to attenuate phagocytosis 3, 8, 9 , proliferation 4 , expression of neurotrophic factor brain-derived neurotrophic factor (BDNF) in hippocampus 10 and apoptosis in microglia 11 .…”

Hypothesizing Darkness Induced Alcohol Intake Linked to Dopaminergic Regulation of Brain Function

“…Review of the old and newer data clearly reveals that within the well-established brain reward circuitry, alcohol metabolites (e.g., dopamine and acetaldehyde) are involved in alcohol induced effects as indicted herein: (1) biologically active metabolites of alcohol can directly or indirectly increase the activity of VTA dopamine neurons, (2) alcohol and alcohol metabolites are reinforcing within the mesolimbic dopamine system, (3) inhibiting the alcohol metabolic pathway inhibits the biological consequences of alcohol exposure, (4) alcohol consumption can be reduced by inhibiting/attenuating the alcohol metabolic pathway in the mesolimbic dopamine system, (5) alcohol metabolites can alter neurochemical levels within the mesolimbic dopamine system, and (6) alcohol interacts with alcohol metabolites to enhance the actions of both compounds (Deehan, Hauser, Wilden, Truitt, & Rodd, 2013). Accordingly, there is a positive relationship between alcohol and alcohol metabolites in regulating the alcohol intake, and these biological consequences lead to an escalation to alcoholism (Deehan, Brodie, & Rodd, 2013).…”

“…Accordingly, there is a positive relationship between alcohol and alcohol metabolites in regulating the alcohol intake, and these biological consequences lead to an escalation to alcoholism (Deehan, Brodie, & Rodd, 2013). Furthermore, fortification of these results has adequately shown that salsolinol can induce dopamine release in the mesolimbic brain region, supporting earlier indications (Hipolito, Sanchez-Catalan, Granero, & Polache, 2009; Melchior, Simpson, & Myers, 1978).…”

“…Thus, during darkness, dopaminergic expression is reduced and this could be responsible in part for our previous findings involving darkness-induced ethanol intake (Blum, et al, 1973; Reiter, et al, 1973, 1974). This notion is fortified by their additional finding that exposure of the short-day photoperiod induced the synthesis of new dopaminergic neurons that “rescued” the resultant behaviors observed during the dark phase (Dulcis, et al, 2013). …”