Are 5-HT receptors involved in the sprouting of serotoninergic terminals following neonatal 5,7-dihydroxytryptamine treatment in the rat?
The neonatal administration of 5,7-dihydroxytryptamine to rats (100 mg kg(?1) s.c. on the 1st and 2nd day after birth) resulted in marked reductions in serotoninergic presynaptic markers ([(3)H]-5-HT synaptosomal uptake, tryptophan hydroxylase activity and endogenous 5-HT content) in various forebrain areas, particularly the cerebral cortex and the hippocampus. In contrast, this treatment produced an increased outgrowth of serotoninergic terminals in the brain stem as judged by the significant increments of these presynaptic markers in this region. Both in the hippocampus and the brain stem, these 5,7-dihydroxytryptamine-induced changes in serotoninergic innervation were associated with a transient increase in 5-HT-sensitive adenylate cyclase activity. No significant alteration of the specific high affinity binding of [(3)H]-5-HT to synaptosomal membranes from various brain regions was detected in 5,7-dihydroxytryptamine-treated rats for at least the first postnatal month. The chronic blockade of 5-HT receptors by metergoline (5 mg kg(?1) day(?1) from day 3 to day 22 after birth) altered neither the changes in presynaptic markers nor the evolution of [(3)H]-5-HT high affinity binding in 5,7-dihydroxytryptamine-treated rats. These findings further illustrate that the high affinity binding sites for [(3)H]-5-HT do not correspond to postsynaptic 5-HT receptors coupled to adenylate cyclase in the rat brain. Apparently, 5-HT receptors play no role in the increased outgrowth of serotoninergic systems in the brain stem following neonatal 5,7-dihydroxy-tryptamine treatment.
Hamon
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Groupe NB, INSERM U.114, Collège de France, 11 place Marcelin Berthelot, 75231 Paris cedex 5, France.
Nelson
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DL
Mallat
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Bourgoin
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