title: The role of the α7 subunit of the nicotinic acetylcholine receptor on motor coordination in mice treated with methyllycaconitine and anabasine.
abstract: The adverse effects of methyllycaconitine (MLA) have been attributed to competitive antagonism of nicotinic acetylcholine receptors (nAChR). Research has indicated a correlation between the LD50 of MLA and the amount of α7 nAChR in various mouse strains, suggesting that mice with more α7 nAChR require more MLA to be poisoned. However, recent research demonstrated that there was no difference in the acute lethality (LD50 ) to MLA in mice lacking the α7 nAChR subunit compared with wild-type mice. The objective of this study was to determine if the α7 nAChR subunit plays a role in motor coordination deficiencies that result from exposure to nAChR antagonists and agonists. We compared the motor function and coordination in wild-type mice to mice lacking the α7 subunit of the nAChR, after treating them with a non-lethal dose of MLA or anabasine, using the following tests: balance beam, grip strength, rotarod, open field and tremor monitor. Analysis of the data indicated that overall there was no difference between the wild-type and knockout mice (P = 0.39 for grip strength; P = 0.21 for rotarod; P = 0.41 for balance beam; P = 0.22 for open field; and P = 0.62 for tremors). Thus results from this study suggest that α7 nAChR does not play an integral role in the acute effects of MLA or anabasine on motor function/coordination. Consequently other subunits of nAChRs found in the neuromuscular junction are likely the primary target for MLA and anabasine resulting in motor coordination deficiencies and acute toxicosis.
authors.affiliation: USDA-ARS Poisonous Plant Research Laboratory, Logan, Utah 84341, USA. Kevin.Welch@ars.usda.gov
authors.forename: K D
authors.initials: KD
authors.lastname: Welch
authors.forename: J A
authors.initials: JA
authors.lastname: Pfister
authors.forename: D R
authors.initials: DR
authors.lastname: Gardner
authors.forename: B T
authors.initials: BT
authors.lastname: Green
authors.forename: K E
authors.initials: KE
authors.lastname: Panter
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives* / Q000633:toxicity; D000691:Anabasine / Q000633:toxicity*; D000818:Animals; D005260:Female; D018737:Hand Strength / Q000502:physiology; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor; C054634:methyllycaconitine; D000691:Anabasine; D000157:Aconitine
keywords: Nicotiana; alpha 7 nicotinic acetylcholine receptor; anabasine; delphinium; larkspur; methyllycaconitine; mice; motor coordination