The K⁺-induced increases in noradrenaline and dopamine release are accompanied by reductions in the release of their intraneuronal metabolites from the rat anterior hypothalamus

Summary

The novel technique of microdialysis has been used to examine the basal and K⁺-induced release of catecholamines and metabolites from the anterior hypothalamus of the urethane-anaesthetized rat in vivo. A high pressure liquid chromatographic assay was developed to simultaneously measure endogenous noradrenaline, dopamine and their intraneuronal metabolites 3,4-dihydroxyphenylglycol (DOPEG) and 3,4-dihydroxyphenylacetic acid (DOPAC) respectively, in each 60 μl dialysate sample. The effect of replacing Ca²⁺ in the perfusion fluid with a low concentration of Cd²⁺, which blocks Ca²⁺ effects, was also studied. Increasing the K⁺ concentration in the perfusion fluid elicited a concentration-dependent increase in noradrenaline and dopamine release. In contrast, there were marked reductions in DOPEG and DOPAC which were not concentration-dependent. In the Ca²⁺-depleted conditions, the K⁺-induced increase in amine release was significantly attenuated, but the reductions in the metabolites were not affected. We suggest that the mechanisms contributing to the observed reductions in the metabolites may be inhibition of neuronal reuptake, an increase in neuronal efflux, an enhancement of vesicular uptake and a decrease in vesicular efflux.