Intraventricular microdialysis: a new method for determining monoamine metabolite concentrations in the cerebrospinal fluid of freely moving rats

Abstract

A new method is described to estimate the cerebrospinal fluid (CSF) concentrations of monoamine metabolites (dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA)) in the lateral ventricle of freely moving rats by use of in vivo microdialysis. Both the baseline concentrations of these metabolites and the rate of dopamine (DA) turnover (estimated by the accumulation of total DA metabolites after 200 mg/kg probenecid) were within the range reported when other methods were used to sample CSF. A series of preliminary studies were conducted to demonstrate that this method can be used to repeatedly sample CSF, and to show that the method is sensitive to local changes in dopaminergic activity induced by lesions, drugs or grafts. (1) Unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra produced a significant decrease in the CSF concentrations of DOPAC and HVA ipsilateral to the lesion, relative to the contralateral side or to concentrations in animals without lesions. (2) When left and right lateral ventricles were sampled simultaneously in animals with a unilateral 6-OHDA lesion, haloperidol induced an increase in DOPAC and HVA concentrations in CSF on both sides of the brain. Interestingly, the haloperidol-induced increase in CSF concentrations of DA metabolites was greater adjacent to the intact striatum of rats with unilateral 6-OHDA lesions than in animals with no lesion. (3) Finally, in animals with adrenal medulla tissue grafted into the lateral ventricle there was an increase in the CSF concentration of DOPAC compared to pregraft values or to those of animals with control grafts.