Involvement of Serotonin in the Pathogenesis of Alcohol Addiction

We studied the contents of serotonin (5-HT) in a few brain structures (hypothalamus, midbrain, and neocortex) and in blood of rats with genetically determined preference of either ethanol solution or water as a liquid for drinking (groups preferring ethanol, PE, or preferring water, PW, respectively). Rats of the PE group differed from PW animals by significantly higher levels of 5-HT in the hypothalamus and blood. Peroral introduction of 4 g/kg ethanol into PE rats resulted in rapid (in not more than 15 min) sharp increases in the 5-HT content in the hypothalamus, neocortex, and blood, but 45 min after ethanol introduction the 5-HT contents in the hypothalamus, midbrain, neocortex, and blood noticeably dropped. It is suggested that within this time interval condensation of 5-HT with acetaldehyde (AcAdh, the first metabolite of ethanol oxidation) is intensified. This results in the production of -carbolines, analogs of morphine-like alkaloids, which are ligands of the opioid receptors. Under conditions of the development of alcohol addiction (free access of PE animals to the ethanol solution and water for several months), the content of 5-HT in the brain structures and blood increased in a parallel manner with an increase in the daily consumption of alcohol. Our findings are proof of the significant involvement of the serotoninergic system in the development of the euphoria state after single alcohol consumption and motivation for its consumption in the course of formation of alcohol addiction.