title: Improvement of spontaneous alternation behavior deficit by activation of α4β2 nicotinic acetylcholine receptor signaling in the ganglioside GM3-deficient mice.
abstract: We have reported that in ganglioside GM3-deficient (GM3(-/-)) mice, spontaneous alternation behavior assessed by a Y-maze task was significantly lower, and total arm entries were significantly higher than in wild-type mice. The objective of the present study was to examine the role of nicotinic acetylcholine receptor (nAChR) signaling in impairment of spontaneous alternation behavior of GM3(-/-) mice. Nicotine treatment (0.3, 1.0 mg/kg, s.c.) dose dependently improved the spontaneous alternation deficit without affecting total arm entries in GM3(-/-) mice. The nicotine-induced (1.0 mg/kg, s.c.) improvement was significantly abolished by the nAChR antagonist mecamylamine (1.0 mg/kg, i.p.). The α4β2 nAChR antagonist dihydro-β-erythroidine (2.5, 10.0 mg/kg, i.p.) dose dependently counteracted the nicotine-induced improvement of spontaneous alternation in GM3(-/-) mice, whereas the α7 nAChR antagonist methyllycaconitine (2.5, 10.0 mg/kg, i.p.) did not. In addition, the α4β2 nAChR agonist RJR-2403 (5.0, 10.0 mg/kg, s.c.) dose dependently and significantly improved the spontaneous alternation deficit, whereas the α7 nAChR agonist PNU120596 (0.3, 1.0, 3.0 mg/kg, i.p.) did not. These findings revealed that nicotine improved spontaneous alternation behavior of GM3(-/-) mice via the activation of α4β2, but not α7, nAChR. Thus, the ganglioside GM3 might be responsible for α4β2 nAChR signaling in the spontaneous alternation behavior.
authors.affiliation: Riken Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Kimie
authors.initials: K
authors.lastname: Niimi
authors.forename: Chieko
authors.initials: C
authors.lastname: Nishioka
authors.forename: Tomomi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Eiki
authors.initials: E
authors.lastname: Takahashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.forename: Chitoshi
authors.initials: C
authors.lastname: Itakura
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D005679:G(M3) Ganglioside / Q000172:deficiency*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005679:G(M3) Ganglioside; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2