Nicotine, but neither the alpha4beta2 ligand RJR2403 nor an alpha7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle - PubMed (original) (raw)

Comparative Study

Nicotine, but neither the alpha4beta2 ligand RJR2403 nor an alpha7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle

N P Visanji et al. Neuropharmacology. 2006 Sep.

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 (alpha4beta2 preferring) and (R)-N-(1-azabicyclo[2.2.2.]oct-3-yl)(5-(2-pyridyl)thiopene-2-carboxamide (Compound A; alpha7-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 microg) 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 alpha4beta2 nor alpha7 subtypes alone is sufficient to provide protection.

PubMed Disclaimer

Cited by

Symptomatic and neuroprotective effects following activation of nigral group III metabotropic glutamate receptors in rodent models of Parkinson's disease.
Austin PJ, Betts MJ, Broadstock M, O'Neill MJ, Mitchell SN, Duty S. Austin PJ, et al. Br J Pharmacol. 2010 Aug;160(7):1741-53. doi: 10.1111/j.1476-5381.2010.00820.x. Br J Pharmacol. 2010. PMID: 20649576 Free PMC article.
Neuronal nicotinic receptors as novel targets for inflammation and neuroprotection: mechanistic considerations and clinical relevance.
Bencherif M. Bencherif M. Acta Pharmacol Sin. 2009 Jun;30(6):702-14. doi: 10.1038/aps.2009.37. Acta Pharmacol Sin. 2009. PMID: 19498416 Free PMC article. Review.
The cholinergic mesopontine tegmentum is a relatively neglected nicotinic master modulator of the dopaminergic system: relevance to drugs of abuse and pathology.
Maskos U. Maskos U. Br J Pharmacol. 2008 Mar;153 Suppl 1(Suppl 1):S438-45. doi: 10.1038/bjp.2008.5. Epub 2008 Jan 28. Br J Pharmacol. 2008. PMID: 18223661 Free PMC article. Review.
Cigarette smoke, nicotine and cotinine protect against 6-hydroxydopamine-induced toxicity in SH-SY5Y cells.
Riveles K, Huang LZ, Quik M. Riveles K, et al. Neurotoxicology. 2008 May;29(3):421-7. doi: 10.1016/j.neuro.2008.02.001. Epub 2008 Feb 14. Neurotoxicology. 2008. PMID: 18359086 Free PMC article.
Animal models of Parkinson's disease: a source of novel treatments and clues to the cause of the disease.
Duty S, Jenner P. Duty S, et al. Br J Pharmacol. 2011 Oct;164(4):1357-91. doi: 10.1111/j.1476-5381.2011.01426.x. Br J Pharmacol. 2011. PMID: 21486284 Free PMC article. Review.

Nicotine, but neither the alpha4beta2 ligand RJR2403 nor an alpha7 nAChR subtype selective agonist, protects against a partial 6-hydroxydopamine lesion of the rat median forebrain bundle - PubMed (original) (raw)