Catecholamine release by intracerebral perfusion of 6-hydroxydopamine and desipramine

The rate of catecholamine release at perfusion sites in the diencephalon of the unanesthetized rat during the perfusion of a solution of 6-hydroxydopamine (6-OHDA) or desipramine (DMI). Endogenous stores of norepinephrine (NE) and dopamine (DA) were first tagged by the cerebral microinjection of 14C- or 3H-labelled NE or DA. After successive control perfusates were collected with a push-pull cannula system, 6-OHDA, in a concentration of 5.0, 0.5, or 0.1 mg/ml, was perfused at 20-23 mul/min through a site in the rat'e brain. The compound induced a dose-related release of both NE and DA. In control experiments, 6-OHDA exerted a non-specific releasing effect on 3H-inulin which was not dose dependent. In addition, DMI, an NE reuptake inhibitor in a concentration of 10.0, 2.0 or 0.5 mg/ml, was perfused through 23 sites in the brain following the injection of labelled NE. DMI enhanced the recovery of NE in the push-pull effluent at the 10.0 mg/ml concentration only. However, an augmented efflux of 3H-inulin was also observed during the perfusion of the highest concentration of DMI. These results support the view that 6-OHDA releases catecholamines from endogenous storage sites, but also indicate a strong non-specific releasing action of this compound possibly at extracellular or non-catecholaminergic loci.