PSYCHOMOTOR EFFECTS OF DOPAMINE INFUSION UNDER DECREASED GLUTATHIONE CONDITIONS

Administration of buthionine sulfoximine (BSO) selectively inhibits gl utathione (GSH) biosynthesis, thereby inducing a GSH deficiency. Becau se GSH plays a critical role in intracellular antioxidant defense, dec reased GSH levels in the brain may result in less oxidative stress (OS ) protection. Thus, the pro-oxidant effects of dopamine (DA), which ra pidly oxidizes to Corm reactive oxygen species, may increase, In this study, the behavioral consequences of reduced OS protection were exami ned by administering BSO (3.2 mg in 30 mu l Ringer's solution, intrace rebroventricularly) every other day for 12 d to male Fischer 344 rats, In addition, DA (15 mu l of 500 mu M) was administered every day; whe n 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 behavi or-rod walking, wire suspension, and plank walking-were performed five times during the experiment. BSO + DA administration, but not DA + BS O, impaired performance by decreasing latency to fall in the rod and p lank walk tests compared to a vehicle only (Ringer's) group. Therefore , depletion of GSH with BSO, followed by DA treatment, produced defici ts in psychomotor behavior. These deficits are similar to those seen i n aged rats? suggesting that the oxidation of DA coupled with a reduce d capacity to respond to OS may be responsible for the induction of ag e-related motor behavioral deficits. (C) 1997 Elsevier Science Inc.