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

• 1.1. Hypothalamic noradrenaline (NA), dopamine (DA) and plasma cortiocosterone concentrations were determined after acute morphine administration to both naive and morphine-tolerant rats and during naloxone-induced withdrawal.
• 2.2. 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.
• 3.3. 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.
• 4.4. After naloxone-induced withdrawal, the hypothalamic content of NA was significantly reduced, simultaneously with an increase in plasma corticosterone, while DA content remained unchanged.
• 5.5. These results suggest that the hypothalamic noradrenergic neurons are 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.