FR DISCRIMINATION-TRAINING REVERSES 6-HYDROXYDOPAMINE-INDUCED STRIATAL DOPAMINE DEPLETION IN A RAT MODEL OF LESCH-NYHAN SYNDROME

Five-day-old rats received 6-hydroxydopamine (6-HD; 100 mu g base) or vehicle intracisternally. Striatal and cortical dopamine (DA) and meta bolite levels were then determined when animals were three or 8.5 mont hs of age and the latter rats had been weight-reduced for 5.5 months. In the latter animals these determinations were made 1 month following 4.5 months of home-cage confinement (untrained animals) or of food-ma intained fixed-ratio (FR) discrimination training involving either a s ingle discrimination (performance animals) or incrementally more diffi cult discriminations. Striatal DA levels in 3-month-old and 8.5-month- old (untrained) 6-HD-treated rats were, respectively, only 3% and 11% of those in untrained vehicle-treated animals (controls). Despite such large depletions, striatal DA levels in 6-HD-treated performance rats were 3-fold higher than those in untrained age-matched 6-HD-treated r ats (i.e., were 32% of values in controls) while those in incrementall y trained 6-HD-treated animals were even higher (i.e., were 60% of con trol values). Related changes occurred in levels of most metabolites. However, in incrementally trained rats, striatal 3-methoxytyramine con centrations were 154% of control values. Cortical DA and metabolite le vels were little affected by 6-HD treatment. The present results confi rm and extend our earlier observations suggesting that reversal of 'ir reversible' neonatal 6-HD-induced striatal dopamine and metabolite dep letion can be accomplished by environmental (training) manipulations i n adult rats.