Excretion of catecholamine metabolites following intraventricular injection of 6-hydroxydopamine in the Macaca speciosa

Abstract

Seven non-human primates ( Macaca speciosa) were stereotaxically implanted with Kopf cannulae with the tip being placed at the junction of the lateral and third ventricles. Following a recovery period, 2 24-hr baseline urine specimens were collected from each animal. 4 of the animals were given intraventricular (i. vent.) injections of 1, 2, 4 and 8 mg of 6-hydroxy-dopamineṡHBr (6-OH-DAṡHBr) at 12-hr intervals ( in 1 ml of artifical CSF) and 7 days later a final injection of 16 mg of 6-OH-DAṡHBr. 3 control animals were given artificial CSF + equimolar NaBr injections on a similar schedule. Following the i. vent. injections 24-hr urine specimens were collected at periodic intervals. Urines were assayed for normetanephrine (NM), metanephrine (M), 3-methoxy-4-hydroxy-mandelic acid (VMA), and 3-methoxy-4-hydroxyphenylglycol (MHPG). All animals were sacrificed 16 days after the final i. vent. injections and 14 areas of brain, adrenal gland, heart, and thoracic sympathetic chain were removed and assayed for norepinephrine (NE). It has been found that it is possible with this schedule of injection of 6-OH-DA to produce animals which have significantly reduced levels of brain NE (70% depletion) without decreasing NE in tissues outside the CNS. Such experimental animal preparations should be of particular use in studies in which a separation of peripheral from central noradrenergic systems is desirable. No differences in the excretion of NM, M, VMA, and MHPG between baseline and post-injection periods were found in those animals which were injected with artificial CSF only. In all animals which were given intraventricular 6-OH-DA and in which there was a decrement in brain NE without a depletion of NE in tissues outside the central nervous system, there was a significant decrement in urinary MHPG between the baseline and post-injection periods while no differences in the excretion of NM, M, or VMA were found. Based upon these data calculations were made which suggest that a significant fraction of urinary MHPG has its origin in metabolism of NE in brain.