Selective recovery of striatal 125I-α-conotoxinMII nicotinic receptors after nigrostriatal damage in monkeys

Evidence suggests that nicotinic receptors play a role in nigrostriatal function, a finding that may be relevant to Parkinson's disease. Knowledge of the conditions that regulate nicotinic receptor expression is therefore important. Previous studies showed that several different nicotinic receptors, including alpha-conotoxinMII (alpha-CtxMII)-sensitive receptors, are decreased after nigrostriatal damage. Nigrostriatal dopaminergic terminals also demonstrate a capacity for recovery after lesioning. The present experiments were therefore done to determine whether there were changes in striatal nicotinic receptors with recovery. To address this, we used two well-characterized animal models of nigrostriatal damage produced using the selective dopaminergic neurotoxin 1-methyl4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Studies in mice showed that striatal I-125-alpha-CtxMII, as well as I-125-epibatidine and I-125-A85380 binding sites significantly recovered 1 month after lesioning, suggesting that alpha6* and most likely alpha4* receptors are increased. Experiments were next done in monkeys since striatal I-125-alpha-CtXMII receptors constitute a large percentage of nicotinic receptors and are more vulnerable to nigrostriatal damage in this model that closely mirrors Parkinson's disease. In monkeys allowed to recover from the toxic effects of MPTP for a 1-2 year period, there was a significant improvement in the Parkinson disability score. There was also a reversal in lesion-induced declines in striatal alpha-CtxMII-sensitive receptors, but no significant change in I-125-epibatidine and I-125-A85380 receptors. These findings suggest that alpha3*/alpha6* sites are selectively increased in monkey striatum with recovery. The present data show that recovery Of I-125-alpha-CtXMII receptors occurs in parallel with the dopamine transporter, indicating that these nicotinic receptors sites are localized to presynaptic dopamine terminals in both species. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.