RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 285
OP 292
DO 10.1124/jpet.106.106997
VO 319
IS 1
A1 Tanuja Bordia
A1 Neeraja Parameswaran
A1 Hong Fan
A1 J. William Langston
A1 J. Michael McIntosh
A1 Maryka Quik
YR 2006
UL http://jpet.aspetjournals.org/content/319/1/285.abstract
AB 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