Alcohol and the Brain: Neuronal Molecular Targets, Synapses, and Circuits

Abstract

Ethanol is one of the most commonly abused drugs. Although environmental and genetic factors contribute to the etiology of alcohol use disorders, it is ethanol's actions in the brain that explain (1) acute ethanol-related behavioral changes, such as stimulant followed by depressant effects, and (2) chronic changes in behavior, including escalated use, tolerance, compulsive seeking, and dependence. Our knowledge of ethanol use and abuse thus relies on understanding its effects on the brain. Scientists have employed both bottom-up and top-down approaches, building from molecular targets to behavioral analyses and vice versa, respectively. This review highlights current progress in the field, focusing on recent and emerging molecular, cellular, and circuit effects of the drug that impact ethanol-related behaviors. The focus of the field is now on pinpointing which molecular effects in specific neurons within a brain region contribute to behavioral changes across the course of acute and chronic ethanol exposure.

Keywords: addiction; alcoholism; dependence; ethanol; intoxication; neuroadaptation; synaptic plasticity; synaptic transmission; tolerance; withdrawal.

Figure 1.. Neurotransmitter/Modulator Systems and Molecular Targets of Ethanol

The symbols and definitions shown here are used in Figures 2 and 3.

Figure 2.. Acute Effects of Ethanol on the Hippocampus, Striatum, Cerebellum, Amygdala, and Midbrain

BLA, basolateral amygdala; CeA, central amygdala; DLS, dorsolateral striatum; DMS, dorsomedial striatum; FSI, fast-spiking interneuron; iLTD, Inhibitory long-term depression; LTP, long-term potentiation; LTD, long-term depression; MSN, medium spiny neuron; SN/VTA, substantia nigra/ventral tegmental area. See text and Figure S1 for references related to each letter and highlighted effect.

Figure 3.. Chronic Effects of Ethanol on the Frontal Cortex, Striatum, Hippocampus, Amygdala, and Midbrain

BLA, basolateral amygdala; CeA, central amygdala; core, nucleus accumbens core; DLS, dorsolateral striatum; DMS, dorsomedial striatum; iLTP, inhibitory long-term potentiation; LTP, long-term potentiation; LTD, long-term depression; shell, nucleus accumbens shell; SN/VTA, substantia nigra/ventral tegmental area. See text and Figure S2 for explanation and references related to each letter and highlighted effect.