Neuroleptic-induced striatal damage in rats: a study of antioxidant treatment using accelerometric and immunocytochemical methods

Rationale: Investigators have postulated that neuroleptic medications may a ffect the motor system through the creation of free radicals. Also, structu ral brain changes related to oxidative damage may disrupt normal striatal f unction. Objective: The goals of this study were to examine whether an anti oxidant diet reduced the abnormal movements caused by long-term neuroleptic exposure and to examine structural effects within specific striatal region s in rats. Methods: Rats were given a basal diet or a diet high in antioxid ants for 4 months, and treated with 10 mg/kg fluphenazine decanoate or sesa me seed oil IM every 2 weeks. At baseline and after treatment, head movemen ts were quantified by accelerometry, and immunocytochemically stained choli nergic neurons in the ventrolateral, mediodorsal, and ventromedial regions of the striatum were quantified. Results: Rats treated with fluphenazine ha d significantly lower neuron densities than those that did not receive anti oxidants. Rats exposed to a diet consisting of antioxidants had significant ly higher neuron densities than those that did not receive antioxidants in each of the three regions tested. Rats treated with fluphenazine had a grea ter increase in the number of accelerometric peaks recorded per minute comp ared with untreated animals. The increase in the number of accelerometric p eaks recorded per minute was lower for animals exposed to antioxidant diets compared with unexposed animals. Lastly, there was a significant correlati on between the accelerometric peak change score and cholinergic neuron dens ity in all three regions. Conclusions: Our results suggest that long-term n euroleptic treatment is associated with an increase in head movements and a reduction in ChAT-stained striatal cholinergic neurons and that these abno rmalities are reduced by antioxidants.