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

被引:14
作者
Basura, GJ
Walker, PD
机构
[1] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA
[2] Wayne State Univ, Sch Med, Cellular & Clin Neurobiol Program, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA
来源
MOLECULAR BRAIN RESEARCH | 2000年 / 81卷 / 1-2期
关键词
6-hydroxydopamine; basal ganglia; p-chloroamphetamine; preprotachykinin; preproenkephalin; Parkinson's disease;
D O I
10.1016/S0169-328X(00)00153-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dopamine (DA) depletion in neonatal rodents results in depressed tachykinin and elevated enkephalin gene expression in the adult striatum (STR). Concurrently, serotonin (5-HT) fibers sprout to hyperinnervate the DA-depleted anterior striatum (A-STR). The present study was designed to determine if increased 5-HT release from sprouted terminals influences dysregulated preprotachykinin (PPT) and preproenkephalin (PPE) mRNA expression in the DA-depleted STR. Three-day-old Sprague-Dawley rat pups received bilateral intracerebroventricular injections of vehicle or the DA neurotoxin 6-hydroxydopamine (6-OHDA, 100 mu g). Two months later, rats received a single intraperitoneal injection of vehicle or the acute 5-HT releasing agent p-chloroamphetamine (PCA; 10 mg/kg). Rats were killed 4 h later and striata processed for monoamine content by HPLC-ED and mRNA expression by in situ hybridization within specific subregions of the A-STR and posterior striatum (P-STR). 6-OHDA treatment severely (>98%) reduced striatal DB levels, while 5-HT content in the A-STR was significantly elevated (doubled), indicative of 5-HT hyperinnervation. 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-STR (55-82%). PCA normalized PPT mRNA levels in all regions of the DA-depleted A-STR and P-STR, yet did not alter PPE levels in either dorsal central or medial regions from 6-OHDA alone, but reduced PPE to control levels in the dorsal lateral A-STR. These data indicate that increased 5-HT neurotransmission, following neonatal 6-OHDA treatment, primarily influences PPT-containing neurons of the direct striatal output pathway. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:80 / 91
页数:12
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