7-Nitroindazole Attenuates 6-Hydroxydopamine-Induced Spatial Learning Deficits and Dopamine Neuron Loss in a Presymptomatic Animal Model of Parkinson's Disease

Kristi L. Haik, Deborah A. Shear, Chad Hargrove, Jared Patton, Michelle Mazei-Robison, Michael I. Sandstrom, Gary L. Dunbar

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precede most of the overt motor symptoms, making early diagnosis and treatment interventions difficult. Because PD has been associated with free radicals generated by nitric oxide, this study tested whether treatments of 7-nitroindazole (7NI), a nitric-oxide-synthase inhibitor, could reduce cognitive deficits that often emerge before overt motor symptoms in a presymptomatic rat model of PD. Rats were given intraperitoneal injections of 50 mg/kg 7NI (or vehicle) just before receiving bilateral, intrastriatal injections of the DA-toxin, 6-hydroxydopamine (6-OHDA). The rats were then given a battery of motor tasks, and their learning ability was assessed using a spatial reversal task in a water-T maze. Results indicate that 7NI treatments attenuate 6-OHDA-induced spatial learning deficits and protect against DA cell loss in the SN, suggesting that 7NI may have potential as an early, presymptomatic pharmacotherapy for PD.

Original languageEnglish
Pages (from-to)178-189
Number of pages12
JournalExperimental and Clinical Psychopharmacology
Volume16
Issue number2
DOIs
StatePublished - Apr 2008

Keywords

  • NADPH-diaphorase staining
  • Parkinson's disease
  • dopamine immunohistochemistry
  • spatial learning
  • water T maze

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