Psychomotor effects of dopamine infusion under decreased glutathione conditions.
Administration of buthionine sulfoximine (BSO) selectively inhibits glutathione (GSH) biosynthesis, thereby inducing a GSH deficiency. Because GSH plays a critical role in intracellular antioxidant defense, decreased GSH levels in the brain may result in less oxidative stress (OS) protection. Thus, the pro-oxidant effects of dopamine (DA), which rapidly oxidizes to form reactive oxygen species, may increase. In this study, the behavioral consequences of reduced OS protection were examined by administering BSO (3.2 mg in 30 microl Ringer's solution, intracerebroventricularly) every other day for 12 d to male Fischer 344 rats. In addition, DA (15 microl of 500 microM) was administered every day; when given on the same day as BSO, it was either 1 h after BSO (BSO + DA group) or 1 h before BSO (DA + BSO group). Tests of psychomotor behavior--rod walking, wire suspension, and plank walking--were performed five times during the experiment. BSO + DA administration, but not DA + BSO, impaired performance by decreasing latency to fall in the rod and plank walk tests compared to a vehicle only (Ringer's) group. Therefore, depletion of GSH with BSO, followed by DA treatment, produced deficits in psychomotor behavior. These deficits are similar to those seen in aged rats, suggesting that the oxidation of DA coupled with a reduced capacity to respond to OS may be responsible for the induction of age-related motor behavioral deficits.
Shukitt-Hale
B
B
USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Denisova
N A
NA
Strain
J G
JG
Joseph
J A
JA
D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344
D019328:Buthionine Sulfoximine; D005978:Glutathione; D004298:Dopamine