Modulation by catecholamine of hypothalamus-pituitary-adrenocortical (HPA) axis activity in morphine-tolerance and withdrawal.

1. Hypothalamic noradrenaline (NA), dopamine (DA) and plasma corticosterone concentrations were determined after acute morphine administration to both naive and morphine-tolerant rats and during naloxone-induced withdrawal. 2. Acutely administered morphine (30 mg/kg) significantly increased the plasma level of corticosterone and reduced the NA and DA content in the hypothalamus. Naloxone (1 mg/kg), administered before morphine, blocked the effect of the opiate on both plasma corticosterone and hypothalamic NA concentration. 3. In chronically morphine-treated rats, a challenge dose of morphine (30 mg/kg) neither modified the plasma corticosterone level nor the NA concentration, while DA content was significantly enhanced. 4. After naloxone-induced withdrawal, the hypothalamic content of NA was significantly reduced, simultaneously with an increase in plasma corticosterone, while DA content remained unchanged. 5. These results suggest that the hypothalamic noradrenergic neurons are mainly mainly implicated in the effect of acute morphine on the hypothalamus-pituitary-adrenocortical (HPA) axis and in the tolerance development to this effect. The results also suggest that a hyperactivity of noradrenergic pathways in the hypothalamus would be one of the physiologically relevant mechanisms mediating the neuroendocrine opiate withdrawal at the HPA level.