Neonatal intraspinal 6-hydroxydopamine, 5,7-dihydroxytryptamine or their combination: effects on nociception and morphine analgesia.

Newborn rats received two injections of intraspinal 6-hydroxydopamine (6-OHDA, 10 micrograms) or 5,7-dihydroxytryptamine (5,7-DHT, 8 micrograms preceded by s.c. desmethylimipramine) or a 'cocktail' of both neurotoxins. The two injections were separated by 24 h. When assayed in adulthood, the 6-OHDA rats showed a substantial (about 80%) depletion of spinal norepinephrine (NE) but an elevation of brainstem NE. Conversely, the 5,7-DHT rats showed a modest (about 60%) loss of spinal serotonin (5-HT) but an elevation of brainstem 5-HT. Rats receiving combined 6-OHDA plus 5,7-DHT showed rostro-caudal, decreasing gradients of spinal NE and 5-HT depletions, with the largest loss in the lumbar cord. These depletions were much less than those observed after the respective single neurotoxin treatments. Neither the single nor combined neurotoxin treatments altered the tail-flick analgesia induced by morphine (1.0, 3.0 or 7.5 mg/kg s.c.). Basal nociception, however, was altered by the neurotoxins but in a sexually dimorphic manner. The 6-OHDA lowered baseline tail-flick latencies in females while 5,7-DHT elevated latencies in males. Like the 6-OHDA-only rats, the combined 6-OHDA plus 5,7-DHT lowered latencies in females. We conclude that neither spinal NE nor 5-HT are essential to morphine analgesia but do participate in nociception, seemingly in a sexually dimorphic fashion.