Neuroleptic-induced striatal damage in rats: a study of antioxidant treatment using accelerometric and immunocytochemical methods.
BACKGROUND
Investigators have postulated that neuroleptic medications may affect the motor system through the creation of free radicals. Also, structural brain changes related to oxidative damage may disrupt normal striatal function.


OBJECTIVE
The goals of this study were to examine whether an antioxidant diet reduced the abnormal movements caused by long-term neuroleptic exposure and to examine structural effects within specific striatal regions in rats.


METHODS
Rats were given a basal diet or a diet high in antioxidants for 4 months, and treated with 10 mg/kg fluphenazine decanoate or sesame seed oil IM every 2 weeks. At baseline and after treatment, head movements were quantified by accelerometry, and immunocytochemically stained cholinergic neurons in the ventrolateral, mediodorsal, and ventromedial regions of the striatum were quantified.


RESULTS
Rats treated with fluphenazine had significantly lower neuron densities than those that did not receive antioxidants. Rats exposed to a diet consisting of antioxidants had significantly higher neuron densities than those that did not receive antioxidants in each of the three regions tested. Rats treated with fluphenazine had a greater increase in the number of accelerometric peaks recorded per minute compared with untreated animals. The increase in the number of accelerometric peaks recorded per minute was lower for animals exposed to antioxidant diets compared with unexposed animals. Lastly, there was a significant correlation between the accelerometric peak change score and cholinergic neuron density in all three regions.


CONCLUSIONS
Our results suggest that long-term neuroleptic treatment is associated with an increase in head movements and a reduction in ChAT-stained striatal cholinergic neurons and that these abnormalities are reduced by antioxidants.
Lohr
J B
JB
VA San Diego Healthcare System and Department of Psychiatry, University of California, San Diego, California, USA.
Caligiuri
M P
MP
Manley
M S
MS
Browning
J A
JA
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000633:toxicity*; D001205:Ascorbic Acid / Q000627:therapeutic use; D002452:Cell Count / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology; D005476:Fluphenazine / Q000633:toxicity*; D019416:Head Movements / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009069:Movement Disorders / Q000209:etiology / Q000517:prevention & control*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000627:therapeutic use; D019207:beta Carotene / Q000627:therapeutic use
D000975:Antioxidants; D014150:Antipsychotic Agents; D019207:beta Carotene; D014810:Vitamin E; D002795:Choline O-Acetyltransferase; D001205:Ascorbic Acid; D005476:Fluphenazine