Synaptic effects induced by alcohol.

Acute and chronic EtOH effects on GABAergic and glutamatergic synaptic transmission. a Schematic diagram of a GABAergic synapse, including presynaptic GPCRs that modulate neurotransmitter release, and postsynaptic ionotropic receptors (located both at synapses and extrasynaptically) that mediate fast synaptic transmission. The predominant presynaptic effect of acute EtOH is potentiation of GABA release (most likely by increasing the probability of vesicle fusion). This presynaptic potentiation may involve neuromodulators such as CRF, and activation of presynaptic GPCRs and downstream signaling pathways. Postsynaptically, EtOH potentiates ionotropic GABAA receptor function. Increases in synaptic GABAAR function prolong synaptic responses, while potentiation of extrasynaptic receptors increases tonic current that affects neuronal excitability, b Changes in GABAergic synapses following chronic EtOH exposure. Presynaptically, the release of GABA is decreased. Alterations in levels of neuromodulators that act on GPCRs, as well as altered function of presynaptic GPCRs may contribute to these changes. Postsynaptically, the subunit composition of GABAARs is altered, often including increased synaptic α4-containing receptors, and fewer α1-containing synaptic receptors. Synaptic α4-containing receptors may be less sensitive to acute EtOH, promoting tolerance to synaptic effect of the drug, c Schematic diagram of a glutamatergic synapse on a dendritic spine, including postsynaptic ionotropic receptors that mediate fast synaptic transmission. The predominant effect of acute EtOH is to inhibit ionotropic glutamate receptor function, and all subclasses of these receptors are sensitive to EtOH inhibition. The most potent effects have been observed at kainate and NMDA receptor subtypes, d Changes in glutamatergic synapses following chronic EtOH exposure. Presynaptically, the release of glutamate is enhanced. Postsynaptically, NMDAR function is increased, most likely due to increased receptor density at the synapse. There is also evidence for increased numbers of NR2B-containing NMDARs. There is also evidence of increased volume of the dendritic spine.