IS 5-HYDROXYTRYPTAMINE MEDIATING DESCENDING INHIBITION IN THE NEONATAL RAT SPINAL-CORD THROUGH DIFFERENT RECEPTOR SUBTYPES

The long-lasting descending inhibition of lumbar segmental reflexes in the neonatal rat spinal cord has been investigated in vitro by recording from lumbar ventral roots on stimulation of a single lumbar dorsal root. Descending inhibition was elicited by a single stimulus to the latero-ventral thoracic cord. A number of strategies were used to clarify the role of 5-hydroxytryptamine (5-HT) in inhibiting the monosynaptic reflex, the ipsilateral polysynaptic response and the contralateral fast response evoked on the opposite side of the lumbar cord. The 5-HT uptake inhibitor, citalopram (10 nM), potentiated both short-interval (0.5-2 s) inhibition and long-interval (5-100 s) inhibition of the monosynaptic reflex, and also inhibition of the polysynaptic response 10-100 s after the thoracic stimulus. Inhibition of the monosynaptic reflex was blocked by ketanserin (1 mu M), spiperone (1 mu M) and methiothepin (1 mu M), but not by spiroxatrine (0.1 mu M) or sulpiride (1 mu M). Sumatriptan (20 nM) and methysergide (10 nM) enhanced inhibition of the monosynaptic reflex 0.2-1 s after the thoracic stimulus. It was concluded that 5-HT acting through 5-HT 5-HT2A/2C receptors is the transmitter responsible for monosynaptic reflex inhibition, at intervals of 0.5-100 s, but a stronger stimulus to the thoracic cord may elicit a non-serotonergic component at intervals of 0.1-2 s. There was no unequivocal evidence that endogenous 5-HT activates 5-HT, receptors to produce inhibition. 5-HT acting through 5-HT2A/2C receptors is also responsible for part of the inhibition of the polysynaptic response, but the transmitter(s) responsible for the ketanserin-resistant component of inhibition and for inhibition of the contralateral fast response has still to be identified.