Aggressive behaviour in transgenic mice expressing APP is alleviated by serotonergic drugs.
Transgenic mouse strains were generated that overexpress human APP or clinical mutants of APP. All transgenic mouse strains that over-express APP displayed essentially the same phenotype of disturbed behaviour, differential glutamatergic responses, deficits in maintenance of long-term potentiation and premature death, but formation of amyloid plaques was seen in the highest expressing APP/London transgenic mice only. Apart from cognitive deficits, the APP transgenic mice were characterized by aggressive behaviour, which was pharmacologically alleviated with 8-OH-DPAT and buspirone, two serotonergic agonists. The atypical neuroleptic drug risperidone was equally active in this regard. The data establish an important aspect of the transgenic mice as experimental models for behavioural aspects of Alzheimer's disease, in addition to other early and late symptoms.
Moechars
D
D
Center for Human Genetics, Flemish Institute for Biotechnology (VIB), K.U.Leuven, Belgium.
Gilis
M
M
Kuipéri
C
C
Laenen
I
I
Van Leuven
F
F
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000374:Aggression; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001923:Brain Chemistry / Q000187:drug effects* / Q000235:genetics; D002065:Buspirone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018967:Risperidone / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018967:Risperidone; D002065:Buspirone