Loss of D3 receptors in the zitter mutant rat is not reversed by L-dopa treatment

Jeffrey N. Joyce, T. C. Der, Lynn Renish, Tracy Osredkar, Diane Hagner, Maria Reploge, Shinichi Sakakibara, Shuichi Ueda

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10 Citations (Scopus)

Abstract

In Parkinson's disease (PD) and animal models of parkinsonism the destruction of nigrostriatal (NSB) system results in a marked loss of the dopamine D3 receptor and mRNA in the islands of Calleja (ICj) and the nucleus accumbens shell (NAS). In animal models, it has been reported that both measures are elevated by repeated intermittent administration of L-dopa. However, a large proportion of PD cases are resistant to L-dopa-induced elevation of D3 receptor number. The zitter mutant (Zi/Zi) rat replicates the slow progressive degeneration of the NSB observed in PD and also exhibits a loss of D3 receptor number in the NAS or ICj. To test if this could be reversed with subchronic L-dopa treatment, injections of carbidopa (10 mg/kg ip) were followed an hour later with injection of L-dopa (100 mg/kg ip) twice a day for 10 days. In control Sprague-Dawley (SD) and zitter heterozygote (Zi/-) rats that do not show a loss of D3 receptors with vehicle treatment, L-dopa produced no change in D3 receptor number or in DA terminal density as measured by dopamine transporter (DAT) binding and tyrosine hydroxylase immunoautoradiography (TH-IR). There was a marked loss of DAT and TH-IR in caudate-putamen (CPu) and NA, as well as D3 receptors in NAS and ICj in Zi/Zi rats but no further change with L-dopa treatment. To determine if the resistance to L-dopa-induced increase in D3 receptor was due to a deficiency in expression of cortical BDNF or its receptor, TrkB, in CPu and NAS, we examined BDNF mRNA by ISHH in frontal cortex and TrkB mRNA in frontal cortex, CPu, and NA. The loss of the NSB in the Zi/Zi did not alter levels of BDNF or TrkB mRNA, nor did L-dopa administration alter levels BDNF or TrkB mRNA. Thus, unlike in 6-hydroxydopamine-treated rats, in Zi/Zi rats administered L-dopa does not reverse the loss of BDNF mRNA or lead to an elevation of D3 receptor number.

Original languageEnglish
Pages (from-to)178-189
Number of pages12
JournalExperimental Neurology
Volume187
Issue number1
DOIs
Publication statusPublished - 2004 May 1
Externally publishedYes

Keywords

  • Nucleus accumbens
  • Parkinson's disease
  • Striatum
  • Substantia nigra
  • Tyrosine hydroxylase
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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  • Cite this

    Joyce, J. N., Der, T. C., Renish, L., Osredkar, T., Hagner, D., Reploge, M., Sakakibara, S., & Ueda, S. (2004). Loss of D3 receptors in the zitter mutant rat is not reversed by L-dopa treatment. Experimental Neurology, 187(1), 178-189. https://doi.org/10.1016/j.expneurol.2004.01.012