As our understanding of cellular signaling pathways has advanced, it has become clear that intracellular communication between receptors is critical for the coordinated function of cells. There are multiple receptors expressed in every cell and their signals pass through a common set of downstream effectors distinguished by multiple isoforms with slightly different specificities and activities. The coupling among these pathways causes interactions among the signals sent by the different classes of receptors. Recent molecular pharmacology studies have demonstrated that ethanol acts on several neurotransmitter systems in the brain such as GABA, NMDA, glycine, 5-hydroxytryptamine (5-HT; serotonin) 3, and nicotinic acetylcholine receptors as well as L-type Ca2+ channels and G protein-coupled receptors. Following the direct actions of ethanol on receptors in the brain, a second wave of indirect effects is initiated that subsequently leads to the typical acute behavioral effects of ethanol, ranging from disinhibition to sedation and hypnosis, with increasing concentrations of ethanol. Therefore, a clear understanding of the interactions between neurotransmitter receptors and their signaling pathways is critical for understanding the mechanisms that underlie ethanol tolerance and dependence.
