Figure 1.

Molecular targets and neuromodulators involved in acute presynaptic ethanol actions at GABAergic synapses. A) Schematic diagram of a presynaptic terminal showing suspected sites of ethanol actions that enhance GABA release (*). The main suspected targets are voltage-gated calcium channels, AC, vesicle fusion, PKCε and intracellular Ca²⁺ stores. Neuropeptides, including CRF, eCBs and small molecule neurotransmitters (including feedback vesicular GABA release) can contribute to or modulate ethanol actions on presynaptic GABA release through actions on presynaptic GPCRs. Note that ethanol enhances GABA release in many brain regions, but inhibits release in others. B) Ethanol is thought to stimulate release of neuropeptides (including enkephalins and CRF) and eCBs, presumably from neurons, and these neuromodulators act on presynaptic GPCRs to alter GABA release. Arrows indicate stimulation, cross-ended lines indicate inhibition. AC = adenylyl cyclase, CB1 = cannabinoid type 1 receptor, CRF = corticotrophin-releasing factor, eCB = endocannabinoid, GABA = gamma-aminobutyric acid, GPCR = G protein-coupled receptor, Gαi/o = alpha i/o G protein subunit, Gαs/olf = alpha s/olf subunit of G protein, Gβγ = beta/gamma dimer subunit of G protein, PKA = protein kinase A, PKCε = protein kinase C epsilon,