Autor: |
Charlton, Maura E., Sweetnam, Paul M., Fitzgerald, Lawrence W., Terwilliger, Rosemarie Z., Nestler, Eric J., Duman, Ronald S. |
Zdroj: |
Journal of Neurochemistry; January 1997, Vol. 68 Issue: 1 p121-127, 7p |
Abstrakt: |
Abstract:Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABAAreceptors throughout the CNS. Conceivably, changes in receptor function may be associated with alterations of subunit composition. In the present study, a comprehensive (1–12 weeks) ethanol treatment paradigm was used to evaluate changes in GABAAreceptor subunit expression in several brain regions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippocampus (a region involved in memory/cognition). Expression of α1and α5subunits was regulated by ethanol in a region‐specific and time‐dependent manner. Following 2–4 weeks of administration, cortical and cerebellar α1and α5subunit immunoreactivity was reduced. In the VTA, levels of α1subunit immunoreactivity were significantly decreased after 12 weeks but not 1–4 weeks of treatment. Hippocampal α1subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, α5mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABAAreceptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol. |
Databáze: |
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