SUBSTANCE-P INCREASES RELEASE OF ACETYLCHOLINE IN THE DORSAL STRIATUMOF FREELY MOVING RATS

Little is known about the role that neuropeptides such as substance P play in cell-to-cell interactions in the striatum. The effect of local ly perfused substance P on extracellular acetylcholine (ACh) in the do rsal striatum of awake, freely moving rats was examined using microdia lysis. Neostigmine (1 muM) was included in the perfusate to improve re covery of ACh. Basal extracellular ACh was sensitive to Na+-channel bl ockade with tetrodotoxin (0.3 muM) and Ca2+-channel blockade with MgCl 2 (10 mM) and therefore largely neuronal in origin. Local perfusion wi th 10 and 25 muM substance P for 20 min elevated extracellular ACh by 30% and 51%, respectively. The NK1 receptor antagonist, CP 96,345 (10 muM), which by itself had no effect on extracellular ACh, prevented th e substance P-induced increase in extracellular ACh. These results sug gest that stimulation of NK1 receptors by substance P enhances ACh rel ease in the dorsal striatum and is consistent with anatomical evidence of a substance P-cholinergic circuit in this region.