Electrochemical Studies of the Effects of Substance P on Dopamine Terminals in the Rat Striatum

Abstract The purpose of this study was to investigate the regulation of dopamine (DA) release and clearance by Substance P (SP) in striatum. In vivo high speed chronoamperometric recording techniques, with Nafion-coated carbon-fiber electrodes, were used to evaluate extracellular DA concentrations in urethane-anesthetized Sprague–Dawley rats. SP was locally applied to striatum. Our data indicate that SP can induce DA release in striatum. However, only about half of the striatal sites respond to SP. Readministration of SP to the same site elicited a smaller DA release. These data suggest that SP-evoked release shows tachyphyllaxis and is heterogeneous in the striatum. Lesioning of DA neurons with 6-OHDA into the medial forebrain bundle abolished DA release induced by SP. It has been shown that SP interacts with three different tachykinin receptors. We found that application of the Neurokinin-1 (NK 1 ) agonist [Sar 9 , Met (O 2 ) 11 ]SP, but not the NK 3 agonist senktide, induced DA release, suggesting that SP-induced DA release may be mediated through NK 1 receptors. We further examined SP effects on DA clearance in striatum. We found that pretreatment with SP significantly attenuated extracellular levels of DA after exogeneous application of DA, suggesting that DA clearance is augmented by SP. Taken together, our data demonstrate that substance P facilitates dopamine release and clearance in the striatum.