Manipulations of brain 5-HT levels affect gene expression for BDNF in rat brain

The aim of the present study was to investigate whether changes in brain S- HT concentrations affect the expression of BDNF mRNA in rat brain. Brain 5- HT concentration in the rat was elevated by combined treatment with tranylc ypromine and L-tryptophan, tranylcypromine alone, by a single dose of the 5 -HT releasing agent p-chloroamphetamine (PCA) or by the selective 5-HT reup take inhibitor paroxetine. 5-HT was depleted by either multiple p-chlorophe nylalanine (pCPA) or PCA injections. The extent of 5-HT depletion following pCPA or PCA was monitored using 5-HT immunocytochemistry. BDNF mRNA abunda nce in treated rats and the corresponding vehicle injected control rats was studied by in situ hybridization histochemistry (ISHH). Two hours after th e combined administration of tranylcypromine and L-tryptophan BDNF mRNA abu ndance in the dentate gyrus was significantly decreased but increased in th e frontal cortex. Tranylcypromine alone or a single injection of PCA had si milar effects on BDNF mRNA expression to the combination of tranylcypromine and L-tryptophan, i.e. they caused significant reductions of BDNF mRNA exp ression in dentate gyrus and increased it in frontal cortex. Paroxetine als o reduced BDNF mRNA in DG but was without effect in frontal cortex. Multipl e injections of both pCPA or PCA resulted in marked reductions of 5-HT immu noreactive axons in the hippocampus, pCPA being more effective. Both drugs significantly increased BDNF mRNA abundances in the dentate gyrus. Multiple PCA injections also increased BDNF mRNA expression in parietal cortex, whi le pCPA induced 5-HT depletion was ineffective. These results suggests that 5-HT modulates BDNF mRNA levels in rat brain. (C) 1999 Elsevier Science Lt d. All rights reserved.