title: Nicotinic receptor modulation for neuroprotection and enhancement of functional recovery following brain injury or disease.
abstract: Despite the well-known adverse health effects of tobacco smoking, numerous studies have shown that nicotine, the principal pharmacologically active alkaloid in tobacco smoke, exerts neuroprotective properties in several animal models of neurodegeneration. Furthermore, cigarette smoking appears to significantly reduce the risk of developing Parkinson's disease in human subjects. We review the animal and human studies that investigated possible neuroprotective actions of nicotine and other nicotinic receptor agonists and antagonists. We demonstrate that nicotine is not neuroprotective in all animal models of neurodegenerative disease. In fact, C57Bl/6 mice pretreated with nicotine have an increased sensitivity to 3-nitropropionic acid, a neurotoxin used in mice to mimic some aspects of Huntington's disease. The actions of nicotine on dopamine release may explain the variable effects of nicotine in animal models of Parkinson's and Huntington's diseases. Finally, we focus on some future directions for studies that evaluate neuroprotective properties of nicotinic agonists and antagonists.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, 40536-0082, USA. jpauly@uky.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Pauly
authors.forename: C M
authors.initials: CM
authors.lastname: Charriez
authors.forename: M V
authors.initials: MV
authors.lastname: Guseva
authors.forename: S W
authors.initials: SW
authors.lastname: Scheff
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006801:Humans; D051379:Mice; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009538:Nicotine / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000502:physiology*; D020127:Recovery of Function / Q000187:drug effects*
chemical_list: D018696:Neuroprotective Agents; D011978:Receptors, Nicotinic; D009538:Nicotine