Noradrenergic and dopaminergic activity in the hypothalamic paraventricular nucleus after naloxone-induced morphine withdrawal

Previous research has shown an increase in hypothalamo;pituitary-adrenal ax is activity following naloxone administration to morphine-dependent rats. I n the present study, we investigated the adaptive changes in the noradrenal ine (NA) and dopamine (DA) systems in the hypothalamic paraventricular nucl eus (PVN) during morphine dependence and withdrawal, Additionally, we exami ned the possible change in 3',5'-cyclic adenosine monophosphate (cAMP) leve ls in that nucleus under the same conditions. Rats were made dependent on m orphine by morphine or placebo (naive) pellet implantation for 7 days. On d ay 8, rat groups received an acute injection of saline or naloxone (1 mg/kg subcutaneously) and were decapitated 30 min later. NA and DA content as we ll as their metabolite production in the PVN were estimated by HPLC/ED. Bot h plasma corticosterone levels and cAMP concentration in the PVN were measu red by RIA. Naloxone administration to morphine-dependent rats (withdrawal) induced a pronounced increase in the production of both the NA metabolite MHPG and the DA metabolite DOPAC and an enhanced NA and DA turnover. Furthe rmore, an increase in corticosterone secretion was observed in parallel to the changes in catecholamine turnover. However, no alterations in cAMP leve ls were seen during morphine withdrawal. These results raise the possibilit y that catecholaminergic afferents to the PVN could play a significant. rol e in the alterations of PVN functions and consequently in the pituitary-adr enal response during morphine abstinence syndrome. These data provide furth er support: for the idea of adaptive changes in catecholaminergic neurons p rojecting to the PVN during chronic morphine exposure. Copyright (C) 2000 S . Karger AG, Basel.