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Calcitriol Promotes Augmented Dopamine Release in the Lesioned Striatum of 6-Hydroxydopamine Treated Rats

Abstract

Current therapies for Parkinson’s disease (PD) offer symptomatic relief but do not provide a cure or slow the disease process. Treatments that could halt progression of the disease or help restore function to damaged neurons would be of substantial benefit. Calcitriol, the active metabolite of vitamin D, has been shown to have significant effects on the brain. These effects include upregulating trophic factor levels, and reducing the severity of some central nervous system lesions. While previous studies have shown that calcitriol can be neuroprotective in 6-hydroxydopamine (6-OHDA) rodent models of PD, the present experiments were designed to examine the ability of calcitriol to promote restoration of extracellular dopamine (DA) levels and tissue content of DA in animals previously lesioned with 6-OHDA. Male Fischer-344 rats were given a single injection of 12 µg 6-OHDA into the right striatum. Four weeks later the animals were administered vehicle or calcitriol (0.3 or 1.0 µg/kg, s.c.) once a day for eight consecutive days. Three weeks after the calcitriol treatments in vivo microdialysis experiments were conducted to measure potassium and amphetamine evoked overflow of DA from both the left and right striata. In control animals treated with 6-OHDA and vehicle there were significant reductions in both potassium and amphetamine evoked overflow of DA on the lesioned side of the brain compared to the contralateral side. In animals treated with 6-OHDA followed by calcitriol there was significantly greater potassium and amphetamine evoked overflow of DA from the lesioned striatum compared to that from the control animals. The calcitriol treatments also led to increases in postmortem tissue levels of DA in the striatum and substantia nigra. These results suggest that calcitriol may help promote recovery of dopaminergic functioning in injured nigrostriatal neurons.

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Acknowledgments

This study was supported in part by United States Public Health Service Grants NS60924 and NS75871. None of the authors have a conflict of interest of any type in association with this work.

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Correspondence to Wayne A. Cass.

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Cass, W.A., Peters, L.E., Fletcher, A.M. et al. Calcitriol Promotes Augmented Dopamine Release in the Lesioned Striatum of 6-Hydroxydopamine Treated Rats. Neurochem Res 39, 1467–1476 (2014). https://doi.org/10.1007/s11064-014-1331-1

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Keywords

  • Striatum
  • Substantia nigra
  • Dopamine
  • Calcitriol
  • 6-OHDA
  • GDNF