ELECTROCHEMICAL STUDIES OF THE EFFECTS OF SUBSTANCE-P ON DOPAMINE TERMINALS IN THE RAT STRIATUM

The purpose of this study was to investigate the regulation of dopamin e (DA) release and clearance by Substance P (SP) in striatum. In vivo high speed chronoamperometric recording techniques, with Nafioncoated carbon-fiber electrodes, were used to evaluate extracellular DA concen trations in urethane-anesthetized Sprague-Dawley rats. SP was locally applied to striatum. Our data indicate that SP can induce DA release i n striatum. However, only about half of the striatal sites respond to SP. Readministration of SP to the same site elicited a smaller DA rele ase. These data suggest that SP-evoked release shows tachyphyllaxis an d is heterogeneous in the striatum. Lesioning of DA neurons with 6-OHD A into the medial forebrain bundle abolished DA release induced by SP. It has been shown that SP interacts with three different tachykinin r eceptors. We found that application of the Neurokinin-1 (NK1) agonist [Sar(9), Met (O-2)(11)]SP, but not the NK3 agonist senktide, induced D A release, suggesting that SP-induced DA release may be mediated throu gh NK1 receptors. We further examined SP effects on DA clearance in st riatum. We found that pretreatment with SP significantly attenuated ex tracellular levels of DA after exogeneous application of DA, suggestin g that DA clearance is augmented by SP. Taken together, our data demon strate that substance P facilitates dopamine release and clearance in the striatum. (C) 1998 Academic Press.