Chronic ethanol administration regulates the expression of GABAA receptor alpha 1 and alpha 5 subunits in the ventral tegmental area and hippocampus
Autor: | Ronald S. Duman, Maura E. Charlton, Paul M. Sweetnam, Rosemarie Terwilliger, Lawrence W. Fitzgerald, Eric J. Nestler |
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Rok vydání: | 1997 |
Předmět: |
Male
medicine.medical_specialty Cerebellum Time Factors Tegmentum Mesencephali Protein subunit Central nervous system Blotting Western Hippocampal formation In Vitro Techniques Biochemistry Hippocampus Rats Sprague-Dawley Cellular and Molecular Neuroscience Receptors GABA Internal medicine Parietal Lobe medicine Animals RNA Messenger Receptor Ethanol Chemistry GABAA receptor Frontal Lobe Rats Ventral tegmental area medicine.anatomical_structure Endocrinology nervous system Cerebral cortex |
Zdroj: | Journal of neurochemistry. 68(1) |
ISSN: | 0022-3042 |
Popis: | Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABAA receptors 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 GABAA receptor 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 alpha 1 and alpha 5 subunits was regulated by ethanol in a region-specific and time-dependent manner. Following 2-4 weeks of administration, cortical and cerebellar alpha 1 and alpha 5 subunits immunoreactivity was reduced. In the VTA, levels of alpha 1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1-4 weeks of treatment. Hippocampal alpha 1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, alpha 5 mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABAA receptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol. |
Databáze: | OpenAIRE |
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