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Effects of alcohol on memory

Health effect of alcohol consumption

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Through Ethanol, Chloride and Neuron

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Effects on the hippocampus

Alcohol acts as a general central nervous system depressant, but it also affects some specific areas of the brain to a greater extent than others. Memory impairment caused by alcohol has been linked to the disruption of hippocampal function—particularly affecting gamma-Aminobutyric acid (GABA) and N-methyl-D-aspartate (NMDA) neurotransmission which negatively impacts long-term potentiation (LTP). The molecular basis of LTP is associated with learning and memory. Particularly, damage to hippocampal CA1 cells adversely affects memory formation, and this disruption has been linked to dose-dependent levels of alcohol consumption. At higher doses, alcohol significantly inhibits neuronal activity in both the CA1 and CA3 pyramidal cell layers of the hippocampus. This impairs memory encoding, since the hippocampus plays an important role in the formations of new memories.

Molecular effects on GABA and NMDA receptors

Alcohol also acts as a positive allosteric modulator of GABA receptors, specifically type GABAA. Upon activation, these GABA receptors conduct Cl-, resulting in neuronal hyperpolarization. This hyperpolarization decreases the chance of an action potential occurring and thus, it has an inhibitory effect on neurotransmission in the central nervous system. GABAA receptor subtypes vary in their sensitivities to dosage of alcohol consumed. Furthermore, acute alcohol intake promotes GABAergic neurotransmission via the presynaptic release of GABA, the dephosphorylation of GABAA receptors (increasing GABA sensitivity), and the elevation of endogenous GABAergic neuroactive steroids. Protein kinase C (PKC) has been implicated in differentially modulating the response of the GABAA receptor to alcohol, with effects depending on the PKC isozyme. Alcohol effects have also implicated protein kinase A in affecting GABAA receptor function, such as promoting sensitivity. Enhancement of GABAergic transmission due to alcohol consumption can also be brought about by neuroactive steroids, such as allopregnanolone, which act as GABAA receptor agonists. Both chronic alcohol consumption and alcohol dependence are correlated with the altered expression, properties, and functions of the GABAA receptor that may contribute to alcohol tolerance. There is still much yet to be discovered about alcohol's specific and varying effects on both the GABAA receptor and its subtypes.

At higher doses, ethanol also affects NMDA receptors (NMDARs) by inhibiting the ion current induced by NMDA, a glutamate receptor agonist. This inhibition of synaptic excitation by alcohol has been shown to be dose-dependent (up to a certain point, after which it did not differ by much). Alcohol appears to produce this inhibition by using a site of the NMDAR that is accessible from the extracellular environment. Therefore, this inhibition of an ion current usually produced by NMDAR activation leads to decreased LTP in hippocampal areas. Alcohol negatively affects LTP to a greater degree in immature versus mature animals. In adolescents, alcohol decreases the expression of both the NMDAR NR2A subunit in the hippocampus and the NR1 subunit in the prefrontal cortex. Studies have also found that a decrease in phosphorylation of 2B subunit in the prefrontal cortex, the hippocampus, the nucleus accumbens, and the striatum. NMDARS may be affected by PKA regulation due to the actions of alcohol. Alcohol's effects on GABAA neurotransmission may indirectly inhibit the activity of the NMDAR, and they may contribute to its blockade of LTP induction; however, alcohol's direct effects on NMDAR alone are sufficient for the inhibition of LTP. The varying dose-dependent response to alcohol relies on the combined interactions and responses of the GABAA receptors, NMDARs, and metabotropic glutamate receptors subtype 5 (mGluR5). These changes prevent excitatory synaptic transmissions from occurring, affecting synaptic plasticity and, in turn, memory and learning. However, there is still much yet to be elucidated concerning specific molecular mechanisms of how alcohol affects memory formation.

Effects on other brain regions

Alcohol also impairs and alters the functioning in the cerebellum, which affects both motor function and coordination. It has a notable inhibitory effect on the neurons of the cerebral cortex, affecting and altering thought processes, decreasing inhibition, and increasing the pain threshold. It also decreases sexual performance by depressing nerve centers in the hypothalamus. Alcohol also has an effect on urine excretion via inhibition of anti-diuretic hormone (ADH) secretion of the pituitary gland. Lastly, it depresses breathing and heart rate by inhibiting neuronal functioning of the medulla.

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