title: Quetiapine modulates conditioned anxiety and alternation behavior in Alzheimer's transgenic mice.
abstract: 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.
authors.affiliation: Department of Psychiatry, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Adrien
authors.initials: A
authors.lastname: Tempier
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.forename: Ruiguo
authors.initials: R
authors.lastname: Zhang
authors.forename: Lynda
authors.initials: L
authors.lastname: Kong
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
authors.forename: Huanmin
authors.initials: H
authors.lastname: Luo
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology* / Q000235:genetics; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003987:Dibenzothiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000235:genetics; D004334:Drug Administration Schedule; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology / Q000517:prevention & control; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D000069348:Quetiapine Fumarate; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D013997:Time Factors
chemical_list: D016564:Amyloid beta-Protein Precursor; D014150:Antipsychotic Agents; D019208:Brain-Derived Neurotrophic Factor; D003987:Dibenzothiazepines; C508853:PSEN1 protein, human; D053764:Presenilin-1; D000069348:Quetiapine Fumarate