Studies of the in vivo catabolism of exogenous dopamine as infused through a push-pull cannula implanted in the rat caudate nucleus

Abstract

In this report, using a push-pull perfusion technique, we examined in vivo the effects of exogenous dopamine (DA) on the output of neurochemical substances from the caudate nucleus (CN) of freely behaving rats. Exogenous DA, at concentrations of 10 −5 M, 5 × 10 −5 M and 10 −4 M, in modified Krebs-Ringer phosphate medium (KRP) was infused directly into the CN for 15 min each. Exogenous DA at the doses tested elicited increases in 3,4-dihydroxyphenylacetic acid (DOPAC) output in a dose-dependent manner. In addition, the higher two doses of exogenous DA also induced increases in homovanillic acid (HVA) output from the rat CN. The increases in DOPAC output by 5 × 10 −5 M DA was partially blocked by the inclusion of 10 −3 M nomifensine in KRP. Interestingly, exogenous DA-induced increases in HVA output were little affected by the nomifensine treatment. However, the catabolism of exogenous DA was almost completely eliminated by a prior 6-hydroxydopamine lesion in the ipsilateral substantia nigra. Furthermore, infusions of exogenous DA did not change 5-hydroxyindoleacetic acid output from the CN. In conclusion, our results confirm in vivo that (a) DA catabolic pathway via DOPAC intermediate predominates over the alternative pathway via 3-methoxytyramine, (b) increases in extracellular DA will lead to increases in DOPAC and HVA levels in extracellular space and (c) the majority of the DA is oxidized by intradopaminergic monoamine oxidase.