Simultaneous changes in hypothalamic catecholamine levels and plasma corticosterone concentration in the rat after acute morphine and during tolerance.

The effects of morphine on plasma corticosterone and hypothalamic noradrenaline (NA) and dopamine (DA) content were studied in naive and in morphine-tolerant rats. Acutely administered morphine (30 mg/kg i.p.) significantly increased the plasma levels of corticosterone and significantly reduced the hypothalamic NA and DA content. In chronically morphine-treated rats (subcutaneously implanted with pellets for 7 days), a challenge dose of morphine (30 mg/kg intraperitoneally (i.p.)) did not modify the plasma corticosterone levels and inhibited the morphine-induced decreases in hypothalamic NA and DA content. These results suggest that: (1) In naive rats, the morphine-induced activation of hypothalamus-pituitary-adrenocortical (HPA) axis is mediated by catecholaminergic neurons in the hypothalamus; (2) In tolerant rats morphine did not modify the plasma corticosterone concentrations, presumably by attenuating hypothalamic noradrenergic and dopaminergic activity. (3) Hypothalamic catecholamines have a role in regulating the HPA axis during morphine tolerance.