Stimulated serotonin release from hyperinnervated terminals subsequent to neonatal dopamine depletion regulates striatal tachykinin, but not enkephalin gene expression

Dopamine (DA) depletion in neonatal rodents results in depressed tachykinin and elevated enkephalin gene expression in the adult striatum (STR). Concu rrently, serotonin (5-HT) fibers sprout to hyperinnervate the DA-depleted a nterior striatum (A-STR). The present study was designed to determine if in creased 5-HT release from sprouted terminals influences dysregulated prepro tachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the DA-deple ted STR. Three-day-old Sprague-Dawley rat pups received bilateral intracere broventricular injections of vehicle or the DA neurotoxin 6-hydroxydopamine (6-OHDA, 100 mu g). Two months later, rats received a single intraperitone al injection of vehicle or the acute 5-HT releasing agent p-chloroamphetami ne (PCA; 10 mg/kg). Rats were killed 4 h later and striata processed for mo noamine content by HPLC-ED and mRNA expression by in situ hybridization wit hin specific subregions of the A-STR and posterior striatum (P-STR). 6-OHDA treatment severely (>98%) reduced striatal DB levels, while 5-HT content i n the A-STR was significantly elevated (doubled), indicative of 5-HT hyperi nnervation. Following 6-OHDA, PPT mRNA levels were depressed 60-66% across three subregions of the A-STR and 52-59% across two subregions of the P-STR , while PPE mRNA expression was elevated in both the A-STR (50-62%) and P-S TR (55-82%). PCA normalized PPT mRNA levels in all regions of the DA-deplet ed A-STR and P-STR, yet did not alter PPE levels in either dorsal central o r medial regions from 6-OHDA alone, but reduced PPE to control levels in th e dorsal lateral A-STR. These data indicate that increased 5-HT neurotransm ission, following neonatal 6-OHDA treatment, primarily influences PPT-conta ining neurons of the direct striatal output pathway. (C) 2000 Elsevier Scie nce B.V. All rights reserved.