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Dopamine Agonist 3-PPP Fails to Protect Against MPTP-Induced Toxicity

Abstract

We investigated the neuroprotective effect of the dopamine agonist, 3-PPP [3-(3-hydroxyphenyl)-N-propylpiperidine] against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity. MPTP (30 mg/kg, i.p., twice, 16 h apart) causes significant dopamine depletion in nucleus caudatus putamen (NCP) by 1 week. 3-PPP had no effect on the monoamine oxidase-B activity (MAO-B) activity in NCP. 3-PPP did not affect dopamine uptake, whereas mazindol significantly blocked the uptake of dopamine dose dependently. MPTP-induced behavioral changes in mice were not reduced by pretreatment with 3-PPP. This dopamine agonist did not prevent dopamine depletion caused by MPTP. MPP+ (20 μM) significantly inhibited the cell proliferation of SH-SY5Y dopaminergic neuronal cells. 3-PPP had no effect on the SH-SY5Y neuronal cell growth in culture and did not block the MPP+-induced cytotoxicity. This study shows that the dopamine agonist 3-PPP failed to protect against MPTP-induced dopaminergic neurotoxicity.

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Correspondence to Holly M. Brown-Borg.

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Muralikrishnan, D., Ebadi, M. & Brown-Borg, H.M. Dopamine Agonist 3-PPP Fails to Protect Against MPTP-Induced Toxicity. Neurochem Res 29, 379–384 (2004). https://doi.org/10.1023/B:NERE.0000013740.53483.39

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  • DOI: https://doi.org/10.1023/B:NERE.0000013740.53483.39

  • 3-PPP Hydrochloride
  • MPTP
  • neuroprotection
  • dopamine uptake
  • monoamine oxidase-B activity