European Journal of Pharmacology 1989-07-18

Ca2+ dependence of the amphetamine, nomifensine, and Lu 19-005 effect on in vivo dopamine transmission.

Y L Hurd, U Ungerstedt

Index: Eur. J. Pharmacol. 166(2) , 261-9, (1989)

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Abstract

The present in vivo microdialysis study examined the role of vesicular- and carrier-mediated mechanisms underlying dopamine (DA) release, uptake and metabolism in halothane-anaesthetized rats. Omission of calcium (Ca2+) from the dialysis perfusing medium, thereby reducing the concentration of Ca2+ in the striatal microenvironment necessary for vesicular DA release, attenuated the elevation of DA normally induced by the potent DA uptake inhibitors, nomifensine and Lu 19-005. Consistent with the results of in vitro studies, amphetamine release DA in a Ca2+-independent manner. The release of DA induced by amphetamine could be effectively blocked by nomifensine and Lu 19-005, demonstrating that the in vivo movement of amines occurred via a transport carried-mediated mechanism. Additionally, the inhibition of DA metabolism produced by amphetamine could be reversed or blocked by prior or delayed treatment with DA uptake inhibitors. The results support a bidirectional in vivo capability of the amine transport carrier.