Alcohol Related Changes in Regulation of NMDA Receptor Functions

Abstract

Long-term alcohol exposure may lead to development of alcohol dependence in consequence of altered neurotransmitter functions. Accumulating evidence suggests that the N-methyl-D-aspartate (NMDA) type of glutamate receptors is a particularly important site of ethanol's action. Several studies showed that ethanol potently inhibits NMDA receptors (NMDARs) and prolonged ethanol exposition leads to a compensatory "up-regulation" of NMDAR mediated functions. Therefore, alterations in NMDAR function are supposed to contribute to the development of ethanol tolerance, dependence as well as to the acute and late signs of ethanol withdrawal.A number of publications report alterations in the expression and phosphorylation states of NMDAR subunits, in their interaction with scaffolding proteins or other receptors in consequence of chronic ethanol treatment. Our knowledge on the regulatory processes, which modulate NMDAR functions including factors altering transcription, protein expression and post-translational modifications of NMDAR subunits, as well as those influencing their interactions with different regulatory proteins or other downstream signaling elements are incessantly increasing. The aim of this review is to summarize the complex chain of events supposedly playing a role in the up-regulation of NMDAR functions in consequence of chronic ethanol exposure.

Impact of Drug Addiction on Mental Health

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Activation of N-methyl-d-aspartate receptor downregulates inflammasome activity and liver inflammation via a β-arrestin-2 pathway

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Induced expression of hepatic <i>N</i>-methyl-D-aspartate receptor 2C subunit gene during liver enlargement induced by lead nitrate, a hepatocellular mitogen

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“…An NMDA receptor (NR) 1 subunit forms a complex with each member of NR2 subfamily, and the complex functions as an NMDA receptor (Nagy, 2008;Kalia et al, 2008). More recently, we found superinduced expression of the Grin2c gene encoding the NR2C subunit, a member of the NR2 subfamily, during the development of liver enlargement with hepatocellular hypertrophy in rats treated with phenobarbital (PB), chlofibrate (CF), or piperonyl butoxide (PBO) (Nemoto et al, 2011a).…”