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The Journal of Neuroscience, November 15, 2001, 21(22):9027-9035

Cloning, Expression, and Regulation of a Glucocorticoid-Induced Receptor in Rat Brain: Effect of Repetitive Amphetamine

Danzhao Wang¹, James P. Herman², Laurel M. Pritchard^{2, 3}, Rebecca H. Spitzer^{2, 3}, Rebecca L. Ahlbrand^{2, 3}, Gerald L. Kramer⁴, Frederick Petty⁴, Floyd R. Sallee^{1, 2}, and Neil M. Richtand^{2, 3}

¹ Pharmacology Research Center, Children's Hospital Medical Center, Cincinnati, Ohio 45229, ² Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, ³ Cincinnati Veterans Affairs Medical Center, Psychiatry Service (V116A), Cincinnati, Ohio 45220, and ⁴ Veterans Affairs Medical Center and University of Texas Southwestern Medical Center, Dallas, Texas 75216

Behavioral sensitization to psychostimulants involves neuroadaptation of stress-responsive systems. We have identified and sequenced a glucocorticoid-induced receptor (GIR) cDNA from rat prefrontal cortex. The full-length GIR cDNA encodes a 422 amino acid protein belonging to G-protein-coupled receptor superfamily. Although the ligand for GIR is still unknown, the dendrogram construction indicates that GIR may belong to peptide receptor subfamily (e.g., substance P receptor), with more distant relationship to subfamilies of glycoprotein hormone receptors (e.g., thyrotropin receptor) and biogenic amine receptors (e.g., dopamine receptor). GIR shares 31-34% amino acid identity to the tachykinin receptors (substance P receptor, neurokinin A receptor, and neurokinin B receptor). GIR mRNA is expressed preferentially in brain, and its neuronal expression is relegated to limbic brain regions, particularly in forebrain. GIR transcript levels are increased significantly and persistently in prefrontal cortex for 7 d after discontinuation of chronic amphetamine exposure. The induction of GIR expression by amphetamine is associated with augmented behavioral activation. These findings suggest that modulation of GIR expression may be involved in behavioral sensitization, and GIR may play a role at the interface between stress and neuroadaptation to psychostimulants.

Key words: GIR; seven-transmembrane spanning receptor; mRNA; prefrontal cortex; chronic amphetamine administration; behavioral sensitization

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21229027-09$05.00/0

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