PMID- 24797332
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20151119
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 272
DP  - 2014 Jul 11
TI  - Rivastigmine improves hippocampal neurogenesis and depression-like behaviors via 
      5-HT1A receptor stimulation in olfactory bulbectomized mice.
PG  - 116-30
LID - S0306-4522(14)00358-3 [pii]
LID - 10.1016/j.neuroscience.2014.04.046 [doi]
AB  - Rivastigmine is a non-competitive inhibitor of both acetylcholinesterase (AChE) 
      and butylcholinesterase (BuChE) used to treat mild to moderate dementia in 
      Alzheimer's disease (AD) patients. Although rivastigmine reportedly ameliorates 
      cognitive dysfunction in these patients, its ability to improve Behavioral and 
      Psychological Symptoms of Dementia (BPSD) remains unclear. To determine whether 
      rivastigmine treatment antagonizes depression-like behaviors, we chronically 
      administered rivastigmine (0.1-1.0mg/kg) to olfactory bulbectomized (OBX) mice 
      once a day for 2weeks, starting 2weeks after bulbectomy. Chronic treatment at 0.3 
      or 1.0mg/kg dose dependently and significantly improved depression-like 
      behaviors, as assessed by tail suspension (TST), forced swim (FST), locomotion 
      and novelty-suppressed feeding (NSFT) tests. Importantly, co-administration with 
      WAY-100635 (1.0mg/kg), a 5-HT1A receptor antagonist, but not ketanserin 
      (1.0mg/kg,), a 5-HT2A receptor antagonist, completely blocked 
      rivastigmine-induced anti-depressive effects, suggesting that 5-HT1A receptor 
      stimulation mediates this activity. Consistent with this observation, 
      rivastigmine treatment significantly rescued impaired neurogenesis observed in 
      OBX mice in a 5-HT1A receptor-dependent manner. Furthermore, enhanced protein 
      kinase B (Akt) and extracellular signal-regulated kinase (ERK) phosphorylation 
      seen following rivastigmine treatment was closely associated with improved 
      neurogenesis. These effects were blocked by WAY-100635 but not ketanserin 
      treatment. Finally, we confirmed that 5-HT1A but not 5-HT2A receptor stimulation 
      by specific agonists mimicked rivastigmine-induced anti-depression activity and 
      promoted hippocampal neurogenesis. We conclude that, in addition to enhancing the 
      cholinergic system, rivastigmine treatment restores normal function of the 
      hippocampal serotonergic system, an activity that likely ameliorates depressive 
      behaviors in AD patients.
CI  - Copyright (c) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
FAU - Islam, M R
AU  - Islam MR
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai, Japan.
FAU - Moriguchi, S
AU  - Moriguchi S
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai, Japan.
FAU - Tagashira, H
AU  - Tagashira H
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai, Japan.
FAU - Fukunaga, K
AU  - Fukunaga K
AD  - Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku 
      University, Sendai, Japan. Electronic address: kfukunaga@m.tohoku.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140504
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Phenylcarbamates)
RN  - 0 (Receptor, Serotonin, 5-HT2A)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - PKI06M3IW0 (Rivastigmine)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Depression/*drug therapy
MH  - Hippocampus/*drug effects/metabolism
MH  - Long-Term Potentiation/physiology
MH  - Male
MH  - Mice
MH  - Neurogenesis/*drug effects
MH  - Olfactory Bulb/metabolism/surgery
MH  - Phenylcarbamates/*pharmacology
MH  - Receptor, Serotonin, 5-HT1A/*metabolism
MH  - Receptor, Serotonin, 5-HT2A/metabolism
MH  - Rivastigmine
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - depression
OT  - neurogenesis
OT  - rivastigmine
OT  - serotonin 1A receptor
EDAT- 2014/05/07 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/05/07 06:00
PHST- 2014/01/06 00:00 [received]
PHST- 2014/04/23 00:00 [revised]
PHST- 2014/04/23 00:00 [accepted]
PHST- 2014/05/07 06:00 [entrez]
PHST- 2014/05/07 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - S0306-4522(14)00358-3 [pii]
AID - 10.1016/j.neuroscience.2014.04.046 [doi]
PST - ppublish
SO  - Neuroscience. 2014 Jul 11;272:116-30. doi: 10.1016/j.neuroscience.2014.04.046. 
      Epub 2014 May 4.