Estimation of chronic dopamine release from the caudate nucleus of the Macaca mulatta

Abstract

Using a cup permanently implanted on the antero-lateral surface of the caudate nucleus, attempts were made to study the spontaneous and d-amphetamine induced release of [ 3H]dopamine (DA), which was continuously synthesised from l-[3,5- 3H]-tyrosine in the unanaesthetised Macaca mulatta placed in a restraining chair with freedom of movement of the head and members. The spontaneous release of [ 3H]DA from dopaminergic terminals was detected during the continuous superfusion of the tissue with [ 3H]amino acid in 8 monkeys. In most cases [ 3H]DA release reached a steady state level within 30 min after the onset of superfusion. Similar results were obtained when the experiments with [ 3H]tyrosine were carried out on 3 successive days. In 2 of the cases examined, the quantity of spontaneously released [ 3H]DA during the last 24 or 48 h of a 5–6 day experiment was markedly increased as compared to that observed during previous days; this effect did not appear to be related to changes in the specific activity of tyrosine in the superfusing medium. In 3 monkeys d-amphetamine ( 10 −5 M ) increased the level of [ 3HH]DA release by 15–20 times that of the normal spontaneous release of the transmitter, the effect was less pronounced in 2 other animals exhibiting a higher level of spontaneous [ 3H]DA release. The amphetamine effect could be detected every day in longitudinal studies. For example, in one animal the ratio of the amphetamine-induced [ 3H]DA release to spontaneous [ 3H]DA release varied only from 10 to 15 during a 5 day experiment. This new approach should make possible long term studies on the regulatory processes involved in DA release from dopaminergic terminals of the nigro-neostriatal system in the unanaesthetised primate.