TY - JOUR T1 - Partial Recovery of Striatal Nicotinic Receptors in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Monkeys with Chronic Oral Nicotine JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 285 LP - 292 DO - 10.1124/jpet.106.106997 VL - 319 IS - 1 AU - Tanuja Bordia AU - Neeraja Parameswaran AU - Hong Fan AU - J. William Langston AU - J. Michael McIntosh AU - Maryka Quik Y1 - 2006/10/01 UR - http://jpet.aspetjournals.org/content/319/1/285.abstract N2 - Recent studies in nonhuman primates show that chronic nicotine treatment protects against nigrostriatal degeneration, with a partial restoration of neurochemical and functional measures in the striatum. The present studies were done to determine whether long-term nicotine treatment also protected against striatal nicotinic receptor (nAChR) losses after nigrostriatal damage. Monkeys were administered nicotine in the drinking water for 6 months and subsequently lesioned with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) over several months while nicotine was continued. 125I-Epibatidine, [125I]5-[125I]iodo-3(2(S)-azetidinylmethoxy)-pyridine (A85380), and 125I-α-conotoxinMII autoradiography was performed to evaluate changes in α4β2* and α3/α6β2* nAChRs, the major striatal subtypes. Nicotine treatment increased α4β2* nAChRs by ≥50% in striatum of both unlesioned and lesioned animals. This increase in α4β2* nAChRs was significantly greater in lesioned compared with unlesioned monkey striatum. Chronic nicotine treatment led to a small decrease in α3/α6β2* nAChR subtypes. The decline in α3/α6β2* subtypes, defined using α-conotoxinMII-sensitive 125I-epibatidine or [125I]A85380 binding, was significantly smaller in striatum of nicotine-treated lesioned monkeys compared with unlesioned monkeys. This difference was not observed for α3/α6β2* nAChRs identified using 125I-α-conotoxinMII. These data suggest that there are at least two striatal α3/α6β2* subtypes that are differentially affected by chronic nicotine treatment in lesioned animals. In addition, the results showing an improvement in striatal α4β2* and select α3/α6β2* nAChR subtypes, combined with previous work, demonstrate that chronic nicotine treatment restores and/or protects against the loss of multiple molecular markers after nigrostriatal damage. Such findings suggest that nicotine or nicotinic agonists may be of therapeutic value in Parkinson's disease. The American Society for Pharmacology and Experimental Therapeutics ER -