MODIFICATION BY DESIPRAMINE (DMI) OF THE AVAILABILITY OF NOREPINEPHRINE RELEASED BY RESERPINE IN THE HYPOTHALAMUS OF THE RAT IN VIVO

¹ Psychopharmacology Research Center, Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee

The present investigations were undertaken to determine whether experiments with a push-pull cannula in vivo can furnish information concerning drug-induced changes in the availability of adrenergic neurohumors at central adrenergic effector sites and also to determine whether desipramine (DMI) can alter the metabolic fate of catecholamines released by reserpine from intraneuronal storage sites in the brain. After the intraventricular administration of H³-norepinephrine, the radioactivity released into the perfusate from the hypothalamus decreased with time, while the ratio of deaminated-O-methylated catecholamine metabolites to amines (DOM/A) remained constant. Reserpine increased both the radioactivity in the perfusate and the ratio of DOM/A. The amount of unchanged norepinephrine recovered in the perfusate was, however, only slightly reduced, whereas the amount of normetanephrine was markedly decreased. Reserpine did not enhance the release of C¹⁴-urea into the perfusate. After pretreatment with DMI, reserpine markedly increased the amounts of both norepinephrine and normetanephrine in the perfusate. Since DMI does not inhibit monoamine oxidase, the findings thus suggest that DMI blocks the reuptake of norepinephrine released by reserpine in brain in vivo by inhibiting the amine transport mechanism in the neuronal membrane.