Journal
EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY
Volume 16, Issue 2, Pages 178-189Publisher
AMER PSYCHOLOGICAL ASSOC
DOI: 10.1037/1064-1297.16.2.178
Keywords
Parkinson's disease; dopamine immunohistochemistry; NADPH-diaphorase staining; spatial learning; water T maze
Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR016481] Funding Source: NIH RePORTER
- NCRR NIH HHS [P20 RR 16481] Funding Source: Medline
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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.
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