The effects of substance P and baclofen on motoneurones of isolated spinal cord of the newborn rat.

The effects of substance P (SP) and baclofen were studied in the isolated spinal cord of newborn rats. Potential changes generated in motoneurones were recorded extracellularly from the ventral root (L3-L5). When SP (8 X 10(-5) M) was introduced into the bath, the depolarization of motoneurones began with a delay of 1.1 s. A large part of this delay can be explained as a time needed for SP to reach the site of action on spinal neurones. When the preparation was perfused with artificial cerebrospinal fluid (CSF) containing low Ca (0.1 mM) and high Mg (1.6-3.5 mM), the spinal reflexes induced by dorsal root stimulation and recorded from the corresponding ventral root were completely abolished. The depolarizing action of SP (10(-7) M) on the motoneurones was potentiated in the low-Ca medium, suggesting that SP acts directly on the motoneurones. Baclofen at 10(-6) M depressed the monosynaptic reflex by about 75%. The SP-induced depolarization of motoneurones was greatly depressed by baclofen in both normal and 0.1 mM-Ca mediums. The effects of baclofen (10(-6) M) on the responses to various depolarizing agents were compared with that on the response to SP in artificial CSF containing 0.1 mM-Ca and 1.6-2 mM-Mg. The SP response was reduced by about 80%, whereas the responses to acetylcholine and glycine were not appreciably affected, and those to L-glutamate, GABA and noradrenaline were depressed by 10-22% by baclofen. The results suggest that baclofen blocks transmission at certain primary afferent synapses by antagonizing the action of SP that is released as a transmitter.