Alcohol and central neurotransmission

The study of the relationships between alcohol consumption and central neurotransmission is difficult: they are different from one individual to another, from one neurotransmission system to another and from one cerebral area to another. Moreover, there is no fully satisfactory animal model of alcoholism and the human studies have to cope with a lot of methodological problems. In spite of these difficulties a bidirectional relationship between alcohol and central neurotransmission is well established. Neuronal dysfunctions are the neurobiological basis for the alcohol behaviour, and ethanol craving seems specifically related to hypofunction of the noradrenergic, GABAergic and serotoninergic systems, and maintained by a positive reinforcement mediated by the dopaminergic and opioid systems. Ethanol alters almost all membrane functions, but it behaves essentially like a barbiturate-type GABAergic agonist. In the short-term, it also stimulates central monoaminergic neurotransmissions. With chronic intoxication, membrane tolerance develops, which is the substratum for tolerance and dependence. Concurrently there are adaptative processes and a depletion of the capacities for synthesis of neurotransmitters, therefore a hypofunctioning of all neurotransmission systems. This hypofunctioning is an additive mechanism for tolerance and dependence, pushing the individual into drinking always more alcohol to palliate it; it is sharply revealed during withdrawal, particularly the GABAergic deficiency.