Serotonin 2A receptor regulation of striatal neuropeptide gene expression is selective for tachykinin, but not enkephalin neurons following dopamine depletion

Serotonin (5-HT) 2A receptor-mediated regulation of striatal preprotachykin in (PPT) and preproenkephalin (PPE) mRNAs was studied in adult rodents that had been subjected to near-total dopamine (DA) depletion as neonates. Two months following bilateral 6-hydroxydopamine (6-OHDA) lesion, PPT mRNA leve ls decreased 59-73% across dorsal subregions of the rostral and caudal stri atum while PPE transcripts increased 61-94%. Four hours after a single inje ction of the serotonin 2A/2C receptor agonist, (+/-)-1-(2,5-Dimethoxy-4-iod ophenyl)-2-aminopropane (DOI; I mg/kg), PPT mRNA expression was significant ly increased in DA-depleted rats across all dorsal subregions of the rostra l and caudal striatum as compared to 6-OHDA-treated animals alone. In the i ntact rat, DOI did not influence PPT mRNA levels in the rostral striatum, b ut did raise expression in the caudal striatum where 5-HT2A receptors are p rominent. DOI did not regulate PPE mRNA levels in any striatal sub-region o f the intact or DA-depleted rat. Prior administration of the 5-HT2A/2C rece ptor antagonist, ritanserin (I mg/kg) or the 5-HT2A receptor antagonist, ke tanserin (I mg/kg) completely blocked the DOI-induced increases in striatal PPT mRNA in both lesioned and intact animals. The ability of ketanserin to produce identical results as ritanserin suggests that 5-HT2A receptor-medi ated regulation is selectively strengthened within tachykinin neurons of th e rostral striatum which are suppressed by DA depletion. The selectivity su ggests that 5-HT2A receptor upregulation following DA depletion is capable of regulating tachykinin biosynthesis without influencing enkephalin expres sion in striatal output neurons. (C) 2001 Elsevier Science BY. All rights r eserved.