Dopaminergic activity in transgenic mice underexpressing glucocorticoid receptors: effect of antidepressants.

摘要: Transgenic mice bearing a transgene coding for glucocorticoid receptor antisense mRNA, which partially blocks expression, were used to investigate the long-term effect of hypothalamic-pituitary-adrenal axis dysfunction on brain dopamine transmission. Compared control mice, transgenic animals showed increased amphetamine-induced locomotor activity and concentrations striatal its metabolites dihydroxyphenylacetic acid homovanillic acid. Binding [3H]SCH 23390 [3H]spiperone to, respectively, D1 D2 receptors was in mice. In contrast, autoradiography [3H]GBR 12935 binding transporter decreased mRNA levels this transporter, measured by situ hybridization, remained unchanged substantia nigra pars compacta. The chronic treatment two weeks with amitriptyline or fluoxetine compared No significant changes observed following antidepressant treatment, whereas both antidepressants reduced [3H]raclopride specific receptors. Amitriptyline, but not fluoxetine, level compacta vehicle- amitriptyline-treated From these results we suggest that hyperactive dopaminergic nigrostriatal pathway controls motor Furthermore, corrected