Alterations in the Postnatal Development of Striatal Preprotachykinin but Not Preproenkephalin mRNA Expression in the Serotonin-Depleted Rat

Abstract

We examined the effects of diminished serotonin (5-hydroxytryptamine, 5-HT) levels on the postnatal development of striatal tachykinin and enkephalin neuropeptide systems. Neonatal rats received intracisternal injection of vehicle or the 5-HT neurotoxin 5,7-dihydroxytryptamine (5,7-DHT; 100 pg) on postnatal day 2 followed by sacrifice 1–29 days later. Monoamine analysis by high-performance liquid chromatography with electrochemical detection revealed a drastic reduction of midbrain 5-HT levels, but not norepinephrine or dopamine, as early as 1 day and extending to 29 days following 5,7-DHT injection. Striatal preprotachykinin (PPT) mRNA levels were significantly increased 8 days following injection. However, PPT mRNA amounts failed to remain up-regulated, falling back to or below control levels during the second and third weeks following injection. By day 29, striatal PPT mRNA had normalized to control levels even though 5-HT amounts were still markedly reduced. Throughout the entire time course, striatal preproenkephalin mRNA levels did not significantly differ from control levels. These results suggest that striatal tachykinin, but not enkephalin, neurons may be transiently sensitive to lowered 5-HT neurotransmission during postnatal development.

Eliminating medullary 5-HT neurons delays arousal and decreases the respiratory response to repeated episodes of hypoxia in neonatal rat pups

“…Serotonergic neuronal loss has been described as early as 1 day following CM administration in postnatal rat pups (57,58). In other studies in rat pups in our laboratories, losses of TPH-immunopositive neurons in the RO and RM were evident when DHT was administered into the CM (12).…”