title: Low-dose nicotine facilitates spatial memory in ApoE-knockout mice in the radial arm maze.
abstract: Here, we investigated the effects of nicotine on spatial memory in ApoE-knockout (ApoE-KO) and wild-type (WT) mice in a radial arm maze. Training occurred on three consecutive days and the test was performed on day 4, with one trial per day. Then on day 4, animals were administered nicotine (0.1, 0.25, 0.5, and 1.0 mg/kg) or the antagonist of nicotinic receptors (nAChRs) mecamylamine (MEC 2 mg/kg) alone or together with 0.1 mg/kg nicotine. The number of errors in the first eight choices was recorded. The results were that 0.1 mg/kg nicotine decreased errors in ApoE-KO mice, while 0.1 and 0.25 mg/kg nicotine reduced errors in WT mice, indicating that lower doses of nicotine elicit a memory improvement. In contrast, 1.0 mg/kg nicotine increased errors in WT mice, but not in ApoE-KO mice. MEC alone had no noticeable effect on errors in either strain of mice. However, co-administration of 0.1 mg/kg nicotine and MEC increased errors and reduced the effects of nicotine in WT mice, but not in ApoE-KO mice. Our study found a biphasic effect of nicotine in WT mice: it improves spatial memory at lower doses and impairs it at a higher dose. In ApoE-KO mice, nicotine improves memory at a low dose and has no effect at a higher dose, suggesting that the ApoE deficiency may influence the efficacy of nicotine. Moreover, a reversal of nicotinic effects with MEC was seen in WT mice, indicating the likelihood of the involvement of nAChRs in the spatial-memory response to nicotine.
authors: Department of Neuropsychiatry, Faculty of Medicine, Kagawa University, 1750-1, Ikenobe Miki, Kita, Kagawa 761-0793, Japan.
authors: Ruby
authors: R
authors: Sultana
authors: Kiyoshi
authors: K
authors: Ameno
authors: Mostofa
authors: M
authors: Jamal
authors: Takanori
authors: T
authors: Miki
authors: Naoko
authors: N
authors: Tanaka
authors: Junichiro
authors: J
authors: Ono
authors: Hiroshi
authors: H
authors: Kinoshita
authors: Yu
authors: Y
authors: Nakamura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008464:Mecamylamine / Q000494:pharmacology; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000627:therapeutic use*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; D009538:Nicotine