REPEATED MORPHINE ADMINISTRATION DOWN-REGULATES GLUCOCORTICOID, BUT NOT MINERALOCORTICOID, RECEPTORS IN THE RAT HIPPOCAMPUS

Activation of the hypothalamic-pituitary-adrenal axis (HPA) is known to be an important component of a neuroendocrine response to opiates. Since this axis is under inhibitory control of hippocampal corticosteroid receptors, the present study has been designed to determine the effects of single (20 mg/kg IP) and repeated (from 20 to 100 mg/kg/day, IP, twice a day for 10 days) morphine administration on binding parameters of these receptors. Glucocorticoid (GR) and mineralocorticoid (MR) receptors were examined by an in vitro [H-3]-corticosterone binding in the cytosol from the rat hippocampus, using the selective GR agonist RU 28362 to discriminate between MR and GR. Repeated, but not single, treatment with morphine significantly (by similar to 22%) reduced the density of GR at 2 h and tended to decrease it at 72 h after the last drug injection. The density of MR was unchanged at those time points. No changes in dissociation constants of either type of the receptors were found following single or repeated morphine administration. The plasma corticosterone level was significantly increased 1 h after acute and chronic administration of morphine (382 and 527%, respectively). These results indicate that repeated morphine administration downregulates GR receptors, which may impair the feedback control mechanism of the HPA activity.