Serotonin hyperinnervation and upregulated 5-HT2A receptor expression and motor-stimulating function in nigrostriatal dopamine-deficient Pitx3 mutant mice

Li Li, Guozhen Qiu, Shengyuan Ding, Fuming Zhou

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

The striatum receives serotonin (5-hydroxytryptamine, 5-HT) innervation and expresses 5-HT2A receptors (5-HT2ARs) and other 5-HT receptors, raising the possibility that the striatal 5-HT system may undergo adaptive changes after chronic severe dopamine (DA) loss and contribute to the function and dysfunction of the striatum. Here we show that in transcription factor Pitx3 gene mutant mice with a selective, severe DA loss in the dorsal striatum mimicking the DA denervation in late Parkinson's disease (PD), both the 5-HT innervation and the 5-HT2AR mRNA expression were increased in the dorsal striatum. Functionally, while having no detectable motor effect in wild type mice, the 5-HT2R agonist 2,5-dimethoxy-4-iodoamphetamine increased both the baseline and l-dopa-induced normal ambulatory and dyskinetic movements in Pitx3 mutant mice, whereas the selective 5-HT2AR blocker volinanserin had the opposite effects. These results demonstrate that Pitx3 mutant mice are a convenient and valid mouse model to study the compensatory 5-HT upregulation following the loss of the nigrostriatal DA projection and that the upregulated 5-HT2AR function in the DA deficient dorsal striatum may enhance both normal and dyskinetic movements.

Original languageEnglish (US)
Pages (from-to)236-250
Number of pages15
JournalBrain Research
Volume1491
DOIs
StatePublished - Jan 23 2013

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Receptor, Serotonin, 5-HT2A
Dopamine
Serotonin
Corpus Striatum
Dihydroxyphenylalanine
Serotonin Receptors
Denervation
Transcription Factors
Up-Regulation
Messenger RNA
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Serotonin hyperinnervation and upregulated 5-HT2A receptor expression and motor-stimulating function in nigrostriatal dopamine-deficient Pitx3 mutant mice. / Li, Li; Qiu, Guozhen; Ding, Shengyuan; Zhou, Fuming.

In: Brain Research, Vol. 1491, 23.01.2013, p. 236-250.

Research output: Contribution to journalArticle

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