title: Effect of α₇ nicotinic acetylcholine receptor agonists and antagonists on motor function in mice.
abstract: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated cation channels found throughout the body, and serve to mediate diverse physiological functions. Muscle-type nAChRs located in the motor endplate region of muscle fibers play an integral role in muscle contraction and thus motor function. The toxicity and teratogenicity of many plants (which results in millions of dollars in losses annually to the livestock industry) are due to various toxins that bind to nAChRs including deltaline and methyllycaconitine (MLA) from larkspur (Delphinium) species, and nicotine and anabasine from tobacco (Nicotiana) species. The primary result of the actions of these alkaloids at nAChRs is neuromuscular paralysis and respiratory failure. The objective of this study was to further characterize the motor coordination deficiencies that occur upon exposure to a non-lethal dose of nAChR antagonists MLA and deltaline as well as nAChR agonists nicotine and anabasine. We evaluated the effect of nAChR agonists and antagonists on the motor function and coordination in mice using a balance beam, grip strength meter, rotarod, open field analysis and tremor monitor. These analyses demonstrated that within seconds after treatment the mice had significant loss of motor function and coordination that lasted up to 1 min, followed by a short period of quiescence. Recovery to normal muscle coordination was rapid, typically within approximately 10 min post-dosing. However, mice treated with the nAChR agonist nicotine and anabasine required a slightly longer time to recover some aspects of normal muscle function in comparison to mice treated with the nAChR antagonist MLA or deltaline.
authors.affiliation: USDA/ARS Poisonous Plant Research Laboratory, 1150 E. 1400N., Logan, UT 84341, USA. kevin.welch@ars.usda.gov
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Welch
authors.forename: James A
authors.initials: JA
authors.lastname: Pfister
authors.forename: Flavia G
authors.initials: FG
authors.lastname: Lima
authors.forename: Benedict T
authors.initials: BT
authors.lastname: Green
authors.forename: Dale R
authors.initials: DR
authors.lastname: Gardner
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000633:toxicity; D000691:Anabasine / Q000633:toxicity; D000818:Animals; D004224:Diterpenes / Q000633:toxicity; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009538:Nicotine / Q000633:toxicity; D018722:Nicotinic Agonists / Q000633:toxicity*; D018733:Nicotinic Antagonists / Q000633:toxicity*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
chemical_list: C579166:Chrna7 protein, mouse; D004224:Diterpenes; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C528313:deltaline; C054634:methyllycaconitine; D009538:Nicotine; D000691:Anabasine; D000157:Aconitine