THE MODULATION OF THE MONOSYNAPTIC REFLEX BY SUBSTANCE-P IN THE HEMISECTED SPINAL-CORD PREPARATION OF THE RAT AND GERBIL

The effects of substance P and the selective neurokinin-I receptor ant agonist (+/-)-CP-96,345 have been compared on in vitro spinal cord pre parations from the rat and the gerbil. Substance P produced a concentr ation-dependent depolarization of motoneurons recorded from ventral ro ots of both species. The EC50 values (mu M mean +/- S.E.M.) obtained i n rat (0.95 + 1.0/-0.49) and gerbil (0.47 + 0.26/-0.17) preparations w ere comparable. The mean maximal depolarization (mV mean +/- S.E.M.) e voked in rat (2.07 + 0.26/-0.25) was approximately two-fold greater th an that evoked in gerbil (1.21 + 0.15/-0.14) preparations. In the rat substance P had a biphasic effect (depression followed by potentiation ) on the short latency probably monosynaptic reflex evoked by electric al stimulation of a dorsal root. In gerbil preparations substance P pr oduced only potentiation of the monosynaptic reflex. The EC50 values ( muM mean +/- S.E.M.) for this potentiating action in rat (0.97 + 0.75/ -0.43) and gerbil (0.46+3.6/-0.4) preparations were similar. This pote ntiation demonstrates a positive modulation of an endogenous excitator y probably glutamatergic transmission by substance P in the ventral ho rn of the spinal cord. The depressant phase observed in rat preparatio ns may be related to the relative immaturity of myelination in rat ven tral root fibres compared to the gerbil. The selective neurokinin-1 an tagonist (+/-)-CP-96,345 was one hundred-fold less potent as an antago nist of substance P-induced depolarizations in the rat (pA2 4.69 +/- 0 .18, n = 7) than in the gerbil (pA2 6.79 +/- 0.16, n = 5) spinal cord. This finding suggests that (+/-)-CP-96,345 may not act solely at the neurokinin-1 recognition site. In conclusion this study demonstrates t hat substance P modulates the monosynaptic reflex in the spinal cord p resumably via activation of neurokinin-1 receptors.