Ethanol tolerance and synaptic plasticity.
Current concepts of the mechanisms underlying many of the pharmacological effects of ethanol on the CNS involve disruption of ion channel function via the interaction of ethanol with specific hydrophobic sites on channel subunit proteins. Of particular clinical importance is the development of tolerance and dependence to ethanol, and it is likely that adaptive changes in synaptic function in response to ethanol's actions on ion channels play a role in this process. In this article, Judson Chandler, Adron Harris and Fulton Crews discuss potential mechanisms of ethanol-induced changes in synaptic function that might provide a cellular basis for ethanol tolerance and dependence. It is proposed that multiple mechanisms are involved that include both transcriptional and post-translational modifications in NMDA and GABAA receptors.
Chandler
L J
LJ
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130, USA.
Harris
R A
RA
Crews
F T
FT
D003598:Cytoskeletal Proteins / Q000187:drug effects; D004361:Drug Tolerance / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D010766:Phosphorylation; D011963:Receptors, GABA-A / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000209:etiology*; D013997:Time Factors
D003598:Cytoskeletal Proteins; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D000431:Ethanol