Quetiapine modulates conditioned anxiety and alternation behavior in Alzheimer's transgenic mice.
2013
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.
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