How alcohol acts on the central nervous system to produce intoxication is still poorly understood. In this video, I attempt to summarize current perspectives on the neural effects of alcohol, emphasizing its recognized actions on GABA and glutamate receptors along with some of its systemic effects.
Welcome to 2 minute neuroscience, where I explain neuroscience topics in 2 minutes or less. In this installment I will discuss alcohol.
How alcohol acts in the central nervous system is still poorly understood. Two of the best known effects of alcohol, however, are its actions on GABA and glutamate receptors. Alcohol increases GABA activity at a subtype of the GABA receptor known as GABAa. The mechanism by which this occurs is still not clear, but it is thought that alcohol may act as a positive allosteric modulator, meaning it binds to a site on the receptor that is separate from where GABA binds, and increases the effect GABA has when it binds to the receptor itself. The immediate effect of this action typically is the inhibition of neural firing.
Alcohol also inhibits the activity of glutamate receptors. Again, the mechanism for this is not fully understood but because glutamate is generally excitatory, inhibition by alcohol initially leads to the reduction of neural activity.
A long list of other synaptic actions have been linked to alcohol, including (but not limited to): activation of serotonin receptors, enhancement of glycine receptor function, inhibition of adenosine reuptake, inhibition of calcium channels, activation of potassium channels, and modulation of nicotinic acetylcholine receptor function. It’s not clear, however, how relevant each of these effects are to the human use of alcohol.
There are also some large-scale effects associated with alcohol. For example, alcohol stimulates dopamine transmission in the mesolimbic dopamine pathway–an action thought to be associated with the reinforcement of alcohol consumption. Alcohol affects motor coordination and balance, potentially in part through its influence on neurons in the cerebellum. And it inhibits long-term potentiation and other mechanisms of synaptic plasticity in the hippocampus, which may contribute to its memory-disrupting effects.
Abrahao KP, Salinas AG, Lovinger DM. Alcohol and the Brain: Neuronal Molecular Targets, Synapses, and Circuits. Neuron. 2017 Dec 20;96(6):1223-1238. doi: 10.1016/j.neuron.2017.10.032.
Goldin M, Marshall EJ. 2016. Alcohol: Pharmacokinetics and Pharmacodynamics. In: Wolf K, White J, Karch S, eds. The SAGE Handbook of Drug & Alcohol Studies : Biological Approaches. London: Sage Publications; 2016.