Nicotine, but neither the alpha(4)beta(2) ligand RJR2403 nor an alpha 7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle

N P Visanji, M J O'Neill, S Duty

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Abstract

Although previous studies suggest nicotine protects against a 6-hydroxydopamine (6-OHDA)-induced lesion of the nigrostriatal tract in rats, it is not known whether functional motor recovery occurs or which nicotinic acetylcholine receptor (nAChR) subtypes mediate this effect. These issues were investigated by comparing the effects of the subtype-specific nAChR agonists, RJR2403 (alpha 4 beta 2 preferring) and (R)-N-(I-azabicyclo [2.2.2.]oct-3-yl)(5-(2-pyridyl)thiopene-2-carboxamide (Compound A; alpha 7-selective) and nicotine given 30 min prior to and daily for 14 days after a partial 6-OHDA lesion. In vehicle treated animals, 6-OHDA (6 mu g) produced a 65 +/- 1.8% loss of striatal tyrosine hydroxylase (TH) immunoreactivity in the lesion versus intact hemisphere. This loss was reduced in animals treated with nicotine (0.6 and 0.8 mg kg(-1)), reaching significance at the higher dose (36.6 +/- 3.7% loss; P <0.01 versus vehicle). Treatment with nicotine (0.6 and 0.8 mg kg(-1)) also significantly reduced the number of amphetamine-induced rotations compared to vehicle treatment. In contrast, treatment with RJR2403 (0.2 and 0.4 mg kg(-1)) or Compound A (10 and 20 mg kg(-1)) reduced neither the degree of amphetamine-induced rotations nor the loss of striatal TH immunoreactivity. These data suggest that whilst nicotine is neuroprotective in this partial lesion model, activation of neither the alpha 4 beta 2 nor alpha 7 subtypes alone is sufficient to provide protection. (c) 2006 Elsevier Ltd. All rights reserved
Original languageEnglish
Pages (from-to)506 - 516
Number of pages11
JournalNeuropharmacology
Volume51
Issue number3
DOIs
Publication statusPublished - Sept 2006

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