PMID- 22950914
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20191210
IS  - 1875-5828 (Electronic)
IS  - 1567-2050 (Linking)
VI  - 10
IP  - 2
DP  - 2013 Feb
TI  - Quetiapine modulates conditioned anxiety and alternation behavior in Alzheimer's 
      transgenic mice.
PG  - 199-206
AB  - Quetiapine, an atypical antipsychotic drug, is effective in treating the 
      behavioral and psychological symptoms in Alzheimer's disease (AD). However, it is 
      presently unclear whether quetiapine has beneficial effects on memory and whether 
      the effects of quetiapine on psychological symptoms are associated with its 
      effect on memory in AD. The present study was designed to examine the effect of 
      chronic administration of quetiapine on the conditioned (generalized) anxiety 
      that is related to learning experience of open arm exposure in the elevated 
      T-maze (ETM) test in an amyloid precursor protein (APP)/presenilin 1 (PS1) double 
      transgenic mouse model of AD. In a 2nd experiment, the effect of quetiapine on 
      memory per se was investigated in a Y-maze test in AD mice. Non-transgenic and 
      transgenic mice were treated with quetiapine in drinking water from the age of 2 
      months. After continuous treatment with quetiapine (5 mg/kg/day) for 10 months, 
      mice were tested for conditioned anxiety on the ETM task. After ETM testing, the 
      expression of brain-derived neurotrophic factor (BDNF), a neuroprotective 
      protein, was examined by immunohistochemistry in the basolateral amygdala (BLA) 
      and hippocampus. In the 2nd experiment, the effect of quetiapine (2.5 or 5 
      mg/kg/day) on the short-term memory in AD mice was tested in a Y-maze test. After 
      10 months of administration, quetiapine prevented the decrease of conditioned 
      anxiety and cerebral BDNF in AD mice. In addition, quetiapine also prevented 
      memory impairment in the Y-maze test in AD mice. These findings suggest that the 
      therapeutic mechanism of quetiapine on anxiety in AD may be associated with its 
      beneficial effect on memory and its neuroprotective effect on cerebral BDNF 
      expression.
FAU - Tempier, Adrien
AU  - Tempier A
AD  - Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, 
      Manitoba, Canada.
FAU - He, Jue
AU  - He J
FAU - Zhu, Shenghua
AU  - Zhu S
FAU - Zhang, Ruiguo
AU  - Zhang R
FAU - Kong, Lynda
AU  - Kong L
FAU - Tan, Qingrong
AU  - Tan Q
FAU - Luo, Huanmin
AU  - Luo H
FAU - Kong, Jiming
AU  - Kong J
FAU - Li, Xin-Min
AU  - Li XM
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Alzheimer Res
JT  - Current Alzheimer research
JID - 101208441
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dibenzothiazepines)
RN  - 0 (PSEN1 protein, human)
RN  - 0 (Presenilin-1)
RN  - 2S3PL1B6UJ (Quetiapine Fumarate)
SB  - IM
MH  - Alzheimer Disease/*complications/drug therapy/genetics/pathology
MH  - Amyloid beta-Protein Precursor/genetics
MH  - Analysis of Variance
MH  - Animals
MH  - Antipsychotic Agents/*therapeutic use
MH  - Anxiety/*drug therapy/*etiology/genetics
MH  - Avoidance Learning/drug effects
MH  - Behavior, Animal/*drug effects/physiology
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Dibenzothiazepines/pharmacology/*therapeutic use
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drinking/drug effects/genetics
MH  - Drug Administration Schedule
MH  - Humans
MH  - Learning Disabilities/etiology/prevention & control
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Mice, Transgenic
MH  - Motor Activity/drug effects/genetics
MH  - Mutation/genetics
MH  - Presenilin-1/genetics
MH  - Quetiapine Fumarate
MH  - Reaction Time/drug effects/genetics
MH  - Time Factors
EDAT- 2012/09/07 06:00
MHDA- 2013/09/07 06:00
CRDT- 2012/09/07 06:00
PHST- 2012/11/14 00:00 [received]
PHST- 2012/05/22 00:00 [revised]
PHST- 2012/07/17 00:00 [accepted]
PHST- 2012/09/07 06:00 [entrez]
PHST- 2012/09/07 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
AID - CAR-EPUB-20120830-6 [pii]
AID - 10.2174/1567205011310020010 [doi]
PST - ppublish
SO  - Curr Alzheimer Res. 2013 Feb;10(2):199-206. doi: 10.2174/1567205011310020010.