Decreased behavioral response to intranigrally administered GABAA agonist muscimol in the lactacystin model of Parkinson's disease may result from partial lesion of nigral non-dopamine neurons: comparison to the classical neurotoxin 6-OHDA.

摘要: Lactacystin is a selective UPS inhibitor recently used to destroy dopamine (DA) neurons in animal models of Parkinson's disease (PD). However, both vitro and vivo studies show discrepancies terms the sensitivity non-DA its toxicity. Therefore, our study was aimed examine toxic effect intranigral administration lactacystin on DA rat substantia nigra (SN), compared classic neurotoxin 6-OHDA. Tissue levels striatum SN GABA were also examined. Moreover, behavioral response nigral GABAA receptors locally administered muscimol evaluated these two PD models. We found that 6-OHDA induced strong decrease level lesioned but only slightly reduced SN. A stereological analysis showed neurotoxins highly decreased number SN, while moderately ones. Finally, group, contralateral rotations after intranigrally administrated contrast increased model. Our proves that, although not fully neurons, are much more vulnerable Partial lesion this model may explain agonist muscimol.