Changes in hypothalamic paraventricular nucleus catecholaminergic activityafter acute and chronic morphine administration

The participation of hypothalamic noradrenaline in the expression of neuroe ndocrine signs of morphine withdrawal has been proposed. The present study in rats examined: (1) the relationships between corticosterone secretion an d the possible modifications in noradrenaline and dopamine content and turn over in the hypothalamic paraventricular nucleus after acute and chronic mo rphine administration; (2) the changes in cyclic adenosine monophosphate (c AMP) levels in the paraventricular nucleus after the same treatments. The r esults showed that acute morphine injection in control rats increased corti costerone release, 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) producti on, and noradrenaline turnover. Dopamine turnover in the paraventricular nu cleus was decreased and the cAMP levels remained unchanged. In chronic morp hine-treated rats, there was no elevation in noradrenaline turnover or in c orticosterone secretion, indicating that tolerance developed to the acute e ffects of the opioid. Correspondingly, no alterations in dopamine turnover were observed when chronic morphine-treated rats were compared with control rats acutely injected with morphine. cAMP levels in the paraventricular nu cleus were unchanged during the tolerant state. The results raise the possi bility that noradrenergic afferents play a significant role in the alterati ons of paraventricular nucleus function and pituitary-adrenal axis activity in response to acute and chronic morphine and suggest that these modificat ions are not mediated through adenylate cyclase activation. The present dat a provide further support for the idea of adaptive changes in noradrenergic neurons projecting to the paraventricular nucleus during chronic morphine exposure. (C) 2000 Elsevier Science B.V. All rights reserved.