Abstract

Turnover of dopamine in the intact brain of the unanesthetized rabbit was estimated from the rate of appearance of endogenous homovanillic acid (HVA) in the cerebrospinal fluid (CSF) compartment. The rate of appearance of the dopamine metabolite was determined by isotope dilution during ventriculocisternal perfusion with artificial CSF containing [3H]HVA. Removal of HVA from the perfusate was concomitantly determined and analyzed in terms of bulk absorption, diffusion and active transport. Studies of the effects of pentobarbital and haloperidol showed that application of either drug resulted in increased HVA levels in the cerebrovascular perfusates. Haloperidol caused a 4-fold increase in the rate of appearance of HVA without affecting the processes for metabolite removal, whereas pentobarbital did not alter the rate of appearance of HVA but induced blockage of its active transport from the perfused CSF compartment. The perfusion method permits simultaneous estimations of the rates of appearance and disappearance of monoamine metabolites in the CSF and is therefore suitable for determining whether a change in the metabolite concentration is causally related to a change in its production or removal or both.