Depolarization responses to tachykinin receptor agonists were recorded extracellularly from lumbar ventral roots of spinal cord isolated from neonatal rats (one to eight days post partum). All spinal cords were hemisected in the sagittal plane. In addition, in some hemisected cords, the dorsal horns were removed by means of a further cut, perpendicular to the first. In both hemisected and quadrisected spinal cords, reproducible depolarization responses were induced by low concentrations of the neurokinin-1-selective agonist substance P methylester (10 nM-1-mu-M) or of the neurokinin-3-selective agonist senktide (3-300 nM). On both types of preparation, responses to substance P methylester (1-mu-M) or senktide (300 nM) were of comparable size. The amplitude of the response to senktide (300 nM) was reduced by at least 88% in spinal cord preparations exposed to tetrodotoxin (0.5-mu-M) or to physiological medium containing magnesium chloride (20 mM). In contrast, under either of these conditions, concentration-response curves to substance P methylester were shifted rightward by 2.8-8.5-fold, with little effect on the maximum response. Responses to senktide were blocked selectively by the N-methyl-D-aspartate antagonist 3-[(+/-)-2-carboxypiperazine-4-yl]propyl-1-phosphonic acid (100-mu-M); the antagonist had little effect on substance P methylester-induced depolarization (mean concentration ratio 2.0). These results suggest that in the neonatal rat spinal cord, application of exogenous tachykinin agonists can induce ventral root depolarization by activation of neurokinin-1 and/or neurokinin-3 receptors. The response to stimulation of neurokinin-1 receptors has a major component likely to be due to a direct action at motoneurons. In contrast, ventral root depolarization evoked by stimulation of neurokinin-3 receptors is due, almost exclusively, to an indirect action. The observation that depolarization induced by the neurokinin-3 agonist senktide was not abolished by removal of the dorsal horns is at variance with the finding that in the adult rat, neurokinin-3 binding sites are confined to this region of the spinal cord. An investigation of this paradox is described in the companion paper (Beresford I. J. M., et al. (1991) Neuroscience 46, 225-232.)
