Cloning, expression, and regulation of a glucocorticoid-induced receptor in rat brain: Effect of repetitive amphetamine

Behavioral sensitization to psychostimulants involves neuroadaptation of st ress-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 recep tor superfamily. Although the ligand for GIR is still unknown, the dendrogr am construction indicates that GIR may belong to peptide receptor subfamily (e.g., substance P receptor), with more distant relationship to subfamilie s of glycoprotein hormone receptors (e.g., thyrotropin receptor) and biogen ic amine receptors (e.g., dopamine receptor). GIR shares 31-34% amino acid identity to the tachykinin receptors (substance P receptor, neurokinin A re ceptor, and neurokinin B receptor). GIR mRNA is expressed preferentially in brain, and its neuronal expression is relegated to limbic brain regions, p articularly in forebrain. GIR transcript levels are increased significantly and persistently in prefrontal cortex for 7 d after discontinuation of chr onic amphetamine exposure. The induction of GIR expression by amphetamine i s associated with augmented behavioral activation. These findings suggest t hat modulation of GIR expression may be involved in behavioral sensitizatio n, and GIR may play a role at the interface between stress and neuroadaptat ion to psychostimulants.