Role of aging and striatal nitric oxide synthase activity in an animal model of tardive dyskinesia.
The risk of tardive dyskinesia (TD) increases with advancing age. Haloperidol increases striatal oxidative stress and inhibits nitric oxide (NO) synthase (NOS) in vitro. Biological aging is associated with increased oxidative stress and reduced brain NOS activity. This paper has explored aging and striatal NOS activity ex vivo as co-morbid factors in an animal model of TD. Young adult, mature adult and aged rats were treated with water or haloperidol (1.5 mg/kg per day) for 12 weeks. Vacous chewing movements (VCM) were monitored, as was striatal NOS activity. Aging significantly increased spontaneous VCM in mature and aged animals and progressively attenuated NOS activity in both mature adult and aged rats compared to young animals, and numerically lower in aged versus mature adult animals. Haloperidol significantly increased VCM in all age groups, while significantly reducing NOS activity in young and mature adults but not aged. Reduced NOS activity after haloperidol treatment was significantly lower in mature compared to young rats, but only numerically lower in aged rats receiving the drug, with a slight increase noted in the latter. In the current model, aging did not markedly alter haloperidol-induced VCM. Abrogated striatal nitrergic activity, therefore, underlies aging and haloperidol-induced VCM. Compensatory nitrergic mechanisms may preclude progressive NOS suppression and dyskinesia under conditions of advanced age and NOS inhibition.
Harvey
Brian H
BH
School of Pharmacy, University of Potchefstroom, North West Province 2520, Potchefstroom, South Africa. fklbhh@puknet.puk.ac.za
Nel
Ané
A
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D015897:Comorbidity; D003342:Corpus Striatum / Q000201:enzymology* / Q000378:metabolism; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000009:adverse effects; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology; D006220:Haloperidol / Q000009:adverse effects; D008297:Male; D008409:Mastication / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018492:Dopamine Antagonists; D019001:Nitric Oxide Synthase; D006220:Haloperidol