Effects of morphine and U-50,488H on neurochemical activity of the hypothalamic noradrenergic neurons and pituitary-adrenal response.

We examined the ability of morphine and U-50,488 H administered acutely to the rat to modify the hypothalamic noradrenaline (NA) content and turnover as well as corticosterone release. Hypothalamic NA and its metabolite 3-methoxy-4-hydroxy-phenylethylen glycol (MHPG) were determined by high-performance liquid chromatography (HPLC). Plasma corticosterone was measured by radioimmunoassay (RIA). The administration of morphine (30 mg/kg i.p.) induced a decrease in the hypothalamic content of NA, with an enhancement in the MHPG and the MHPG/NA ratio. Similarly, the administration of U-50,488 H (15 mg/kg i.p.) produced an increase in the MHPG and MHPG/NA ratio without any changes in the NA content. The present results also show that corticosterone secretion was increased after acute morphine or U-50,488 H, in parallel with an enhanced NA turnover and strongly suggest that noradrenergic neurons have stimulatory effects on the HPA axis activity, reflecting an indirect action of opioid on the axis through hypothalamic catecholaminergic systems.