Page - (000193) - in Biomedical Chemistry: Current Trends and Developments

exposure to psychostimulants or depressants. Acute exposure to alcohol increases the inhibitory effect of GABAA receptors, and enhances other inhibitory modulators, decreasing also the function of excitatory neurotransmitters. Prolonged drinking has the opposite effect, decreasing GABAA receptor function by decreasing receptor levels or altering protein composition. Behaviorally, acute alcohol consumption translates into a range of dose-dependent effects that scale from social disinhibition to impaired motor control and decision-making, followed by mild to severe ataxia and hippocampal dysfunction, and eventually ending in sedation, coma, cardiac arrest and possible death (Tabakoff, 1996; 2013; Gilpin, 2008; Koob, 2014). Chronic exposure to alcohol leads to compensatory adaptations in the reward circuitry, and to the development of alcohol related behaviors, such as tolerance, meaning that over time one will need a higher alcohol dose to obtain the same reward effect. When alcohol consumption is discontinued, several withdrawal effects occur, such as tremors, seizures, insomnia, and confusion. These effects may result from the hyperactive adaptations suffered under prolonged use that are no longer balanced by the alcohol inhibitory effects. The consequent increase in glutamatergic activity may lead to toxicity and cell death (Becker, 2014). Under chronic exposure to psychostimulants the GABAergic component of the reward system is also deeply affected, reduced GABAergic inhibition of the dopaminergic mesocorticolimbic pathway contributes to addiction by disrupting the frontal cortical circuits that regulate motivation, drive, and self-control, increasing the motivational salience of drug-associated stimuli (Volkow, 2002) 2.4.4 Gliotransmitters The communication between neurons and astrocytes through the so- called gliotransmitters (such as glutamate, ATP, and D-serine) has been shown to modulate synaptic transmission and plasticity through several mechanisms (Araque, 2014). Research in the field of neuron-glia interactions has gained relevance over the last few years, revealing the involvement of astrocytes and microglia directly at the synaptic cleft. It is now clear that astrocytes and microglia play multiple roles in brain