Quetiapine modulates anxiety-like behaviours and alleviates the decrease of BDNF in the amygdala of an APP/PS1 transgenic mouse model of Alzheimer’s disease
Quetiapine, an atypical antipsychotic drug, is effective in treating the behavioural and the psychological symptoms of dementia (BPSD). The objective of this study was to examine the effects of quetiapine on anxiety-like behaviour in the amyloid precursor protein (APP)/ presenilin 1 (PS1) double transgenic mouse model of Alzheimer’s disease (AD). The mice were treated with quetiapine (0, 2.5, or 5 mg/kg/day) orally in drinking water for 7 or 10 months starting from 2 months of age. Conditioned anxiety was measured using the elevated T-maze (ETM). To measure memory, the Y-maze and the Morris Water maze were employed. After behavioural testing, β-amyloid (Aβ) plaques in the hippocampus and cortex of transgenic mice were stained using Congo Red. Brain-derived neurotrophic factor (BDNF) in the basolateral amygdala (BLA) and the hippocampus of mice was examined using immunohistochemical methods. The statistics revealed an interaction between quetiapine and APP/PS1 double transgenic mice in the avoidance phase of the ETM. Quetiapine modulates anxiety-like behaviours in the ETM. The anxiety-like behaviours were associated with reductions in BDNF levels in the BLA and hippocampus of the transgenic mice. This was reversed by treatment with quetiapine. Furthermore, chronic administration of quetiapine attenuated the memory impairment and decreased the Aβ plaque load in the brain. This study demonstrates that quetiapine normalizes anxiety-like behaviour and up-regulates cerebral BDNF levels in the APP/PS1 mice, suggesting that quetiapine may function as a neuroprotectant as well as an antipsychotic in treating the BPSD associated with AD.
Alzheimer’s disease, APP/PS1 transgenic mouse, Quetiapine, Anxiety, Amygdala, Brain derived neurotrophic factor, Memory, Hippocampus
Master of Science (M.Sc.)