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Chronic Ethanol Administration Alters Immunoreactivity for GABA A Receptor Subunits in Rat Cortex in a Region‐Specific Manner
Author(s) -
Grobin A. Chistina,
Fritschy JeanMarc,
Morrow A. Leslie
Publication year - 2000
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2000.tb02076.x
Subject(s) - piriform cortex , immunohistochemistry , endocrinology , medicine , prefrontal cortex , cortex (anatomy) , cingulate cortex , receptor , posterior parietal cortex , protein subunit , biology , chemistry , hippocampus , central nervous system , neuroscience , biochemistry , cognition , gene
Background: Chronic ethanol administration has a plethora of physiological effects. Among the most consistently observed findings is a change in the expression pattern of γ‐aminobutyric acid type A (GABA A ) receptor subunits in the rat brain cortex. These findings led to the hypothesis of “subunit substitution” to account for changes in receptor function without changes in receptor number. Methods: We used subunit (α1 and α4) specific antibodies and a combination of immunohistochemistry and immunoblotting to examine subregions of cortex (prefrontal, cingulate, motor, parietal, and piriform) for their response to 2 weeks of forced ethanol administration. Results: Overall, cortical immunoreactivity for the α1 subunit was decreased and for the α4 subunit increased whether measured immunohistochemically or by immunoblotting. Piriform cortex exhibited a bidirectional change in GABA A receptor α1 and α4 immunoreactivity, similar to that previously observed in preparations of whole cortex. However, in parietal cortex, declines in α1 immunoreactivity (55 ± 12% control value [CV] and 88.3 ± 4.3% CV; immunohistochemistry and immunoblotting, respectively) were not accompanied by concomitant increases in α4 immunoreactivity (104 ± 8% CV and 116 ± 9.3% CV; immunohistochemistry and immunoblotting, respectively). Conversely, α4 immunoreactivity increased in cingulate cortex (210 ± 30% CV and 134 ± 9.5% CV; immunohistochemistry and immunoblotting, respectively) without a decline in α1 immunoreactivity (90 ± 4% CV and 91.3 ± 3.9% CV; immunohistochemistry and immunoblotting, respectively). Prefrontal and motor cortex exhibited GABA A receptor subunit peptide alterations, but these changes varied with the method of analysis. Conclusions: These findings demonstrate that ethanol dependence results in nonuniform changes in GABA A receptor subunit peptide levels across the rat brain cortex and suggest that mechanisms which subserve functional changes in receptor activity may vary in accordance with anatomic or cellular differences within the cortex.