7-nitroindazole attenuates 6-hydroxydopamine-induced spatial learning deficits and dopamine neuron loss in a presymptomatic animal model of Parkinson's disease.
Parkinson's disease (PD) is a neurodegenerative disorder in which loss of dopaminergic (DA) neurons (>50%) in the substantia nigra (SN) precedes 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.
Haik
Kristi L
KL
Department of Biological Sciences, Northern Kentucky University, Highland Heights, KY 41099, USA. haikk@exchange.nku.edu
Shear
Deborah A
DA
Hargrove
Chad
C
Patton
Jared
J
Mazei-Robison
Michelle
M
Sandstrom
Michael I
MI
Dunbar
Gary L
GL
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007191:Indazoles / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D013378:Substantia Nigra / Q000473:pathology
D007191:Indazoles; D018696:Neuroprotective Agents; D009249:NADP; D016627:Oxidopamine; C080122:7-nitroindazole; D004298:Dopamine