The GABAA Receptor Complex as a Target for Fluoxetine Action |
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Authors: | Tunnicliff G Schindler N L Crites G J Goldenberg R Yochum A Malatynska E |
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Institution: | (1) Departments of Biochemistry and Molecular Biology, and Pharmacology and Toxicology, Indiana University School of Medicine, 8600 University Boulevard Evansville, IN, 47712 |
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Abstract: | The clinically important antidepressant fluoxetine is established as a selective serotonin reuptake inhibitor. This study demonstrates that fluoxetine also interacts with the GABAA receptor complex. At concentrations above 10 M fluoxetine inhibited the binding of both 3H]GABA (IC50 = 2 mM) and 3H]flunitrazepam (IC50 = 132 M ) to the GABAA receptor complex in brain cortical membranes. Low fluoxetine concentrations (1 nM) enhanced GABA-stimulated Cl– uptake by a rat cerebral cortical vesicular preparation. At higher concentrations (100 M and 1 mM), however, fluoxetine inhibited GABA-stimulated Cl– uptake, an effect related to a reduction in Emax. These observations might assist in an explanation of the basis of the antidepressant action of fluoxetine. |
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Keywords: | GABAA receptor complex GABA chloride channel fluoxetine antidepressants diazepam flunitrazepam |
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