EVIDENCE FOR MODULATORY EFFECTS OF SUBSTANCE-P FRAGMENTS (1-4) AND (8-11) ON ENDOGENOUS DOPAMINE OUTFLOW IN RAT STRIATAL SLICES

The effects of substance P-(1-4) and substance P-(8-11) on endogenous dopamine outflow in rat striatal slices were investigated. The dose-re sponse curves (0.01 nM to 1 mu M) were bell-shaped for both peptides, with significant increases in dopamine outflow at 0.1 and 1 nM. Dopami ne overflow elicited by 1 nM substance P-(1-4) or substance P-(8-11) a nd 25 mM KCl was additive. Although substance P-(8-11) contains a trun cated tachykinin sequence, the tachykinin NK1 receptor antagonist WIN 51 708 (17 beta-hydroxy-17 alpha-ethynyl-5 lpha-androstano[3,2-b]pyrim ido[1,2-a]benzimidazole (2.5 nM) fully reversed its effect. The intera ction between the antagonist and 1 nM substance P-(1-4) was statistica lly not significant. The data constitute the first evidence that the f ragments substance P-(1-4) and substance P-(8-11) could exert central effects and suggest that they may play a role in neuromodulation in th e basal ganglia.