Possible Interaction: Ethanol and Gamma-Aminobutyric Acid

“BACKGROUND Ethanol modulates glutamate and γ-aminobutyric (GABA) function.”

“ Alcohol … GABA release in the CeA and alcohol dependence is characterized by increased baseline GABA release in CeA. Interestingly, GABA release in Nf1(+/-) mice is greater …-type mice, is not elevated by induction of dependence by CIE, and failed to show alcohol-induced facilitation both before and after CIE.”

“Memory processing is thought to involve persistent, use-dependent changes in synaptic transmission, and ethanol alters the activity of multiple signaling molecules involved in synaptic processing, including modulation of the glutamate and gamma-aminobutyric acid (GABA) transmitter systems that mediate most fast excitatory and inhibitory transmission in the brain.”

“These studies have shown that acute ethanol exposure increases GABA release at molecular layer interneuron-to-Purkinje cell synapses and also at reciprocal synapses between molecular layer interneurons.”

“Perturbations in a wide range of neurochemical systems, including glutamate, γ-aminobutyric acid , monoamines, a host of neuropeptide systems, and various ion channels produced by the chronic presence of alcohol ultimately compromise the functional integrity of the brain.”

“Hypotheses are proposed to explain how ethanol interacts with the GPCR pathways to increase GABA release and how this interaction contributes to the brain region specificity of ethanol-enhanced GABA release.”

“The ability of ethanol to increase GABA release can be regulated by different G protein-coupled receptors (GPCRs), such as the cannabinoid-1 receptor, corticotropin-releasing factor 1 receptor, GABA(B) receptor, and the 5-hydroxytryptamine 2C receptor.”

“However, alcohol influences the activity of many transmitter systems including GABA and endogenous opioids and cannabinoids.”

“Based on the similarity of ethanol intoxication to the behavioral effects of drugs known to target gamma-aminobutyric acid type A (GABAA) receptors (GABARs), it has been suspected for decades that ethanol facilitates the activity of GABA.”

“ Ethanol interactions with gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain, play key roles in acute intoxication.”

“Additional factors contributing to the degree to which ethanol interacts with GABA function include an involvement of GABAB and other receptors that influence ethanol-induced GABA release, an effect of phosphorylation on GABA responsiveness, and a regional reduction of glutamatergic tone.”

“While selectivity of ethanol to enhance the effect of GABA was initially attributed an effect on type-1-benzodiazepine (BZD)-GABAA receptors, a lack of ethanol's effect on GABA responsiveness from isolated neurons with this receptor subtype discounted this contention.”