Effects of apomorphine in vitro on the uptake and release of catecholamines in crude synaptosomal preparations of rat striatum and hypothalamus

Abstract It is currently believed that apomorphine exerts its pharmacological effects primarily by a direct stimulatory action on post-synaptic dopaminergic receptors. In the present study, uptake of 3 H-dopamine into crude synaptosomal preparations of rat striatum and uptake of 3 H-norepinephrine into crude synaptosomal preparations of rat hypothalamus were inhibited 50 per cent by concentrations of apomorphine of 3.6 ± 0.5 × 10 −5 M and 3.2 ± 0.2 × 10 −5 M respectively. Lineweaver-Burk plots of 3 H-catecholamine uptake data revealed that apomorphine exhibited mixed inhibition kinetics for dopamine uptake into striatum ( K i = 1.91 ± 0.19 × 10 −5 M) and mixed inhibition kinetics for norepinephrine uptake into hypothalamus ( K i = 2.0 ± 0.17 × 10 −5 M). In crude synaptosomes of rat striatum, apomorphine elicited a dose-dependent release of 3 H-dopamine during a 5-min incubation period at 37°. In contrast, the drug failed to produce a significant release of 3 H-norepinephrine from crude synaptosomes obtained from rat hypothalamus. While these results suggest that apomorphine in high concentrations is capable of inhibiting the uptake of catecholamines and stimulating the release of dopamine at nerve endings, it is unlikely that these events contribute significantly to the behavioral effects elicited in animals after administration of the drug, since such effects occur at much lower doses.