Substance P in the ventral pallidum: projection from the ventral striatum, and electrophysiological and behavioral consequences of pallidal substance P.

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The ventral pallidum of the basal forebrain contains a high concentration of substance P and receives a massive projection from the nucleus accumbens. The present study was designed to determine whether the accumbens serves as a source for substance P-containing fibers in the ventral pallidum and characterize the function of this tachykinin peptide within the ventral pallidum. By combining in situ hybridization for messenger RNA of the substance P prohormone, beta-preprotachykinin, with Fluoro-Gold retrograde labeling from iontophoretic deposits in the ventral pallidum, a population of substance P-containing neurons was demonstrated in the shell and core components of the nucleus accumbens and the ventromedial striatum. The function of substance P within the ventral pallidum was characterized at the level of the single neuron, and the behaving animal. Electrophysiological assessment revealed that approximately 40% of the 97 ventral pallidal neurons tested were readily excited by microiontophoretic applications of substance P or a metabolically stable agonist analog, DiMeC7 [(pGlu5, MePhe8, MeGly9)-substance P5-11]. Response characteristics were distinguished from glutamate-induced excitations by a slower onset and longer duration of action. Recording sites of tachykinin-sensitive neurons were demonstrated to be located throughout the ventral pallidum and within high densities of fibers exhibiting substance P-like immunoreactivity. When behaving rats received microinjections of DiMeC7 into this same region, the animals displayed an increase in motor activity, with a response threshold of 0.1nmol per hemisphere. These results verify the existence of a substantial substance P-containing projection from the nucleus accumbens to the ventral pallidum. The projection likely serves to excite ventral pallidal neurons for these neurons readily increased firing following local exposure to tachykinins. Furthermore, an increase in motor behavior appears to be a consequence of this neuronal response.