TY  - JOUR
AU  - Schneider, F.
AU  - Baldauf, K.
AU  - Wetzel, W.
AU  - Reymann, Klaus
TI  - Effects of methylphenidate on the behavior of male 5xFAD mice.
JO  - Pharmacology, biochemistry and behavior
VL  - 128
SN  - 0091-3057
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - DZNE-2020-04069
SP  - 68-77
PY  - 2015
AB  - Alzheimer's disease is a neurodegenerative disorder characterized by a loss of memory and spatial orientation. It is also reported that the dopamine system is affected. Dopamine plays a prominent role in motor functions, motivation, emotion, arousal and reward, and it is important for learning and memory. One model that represents characteristic hallmarks of Alzheimer's disease is the 5xFAD mouse model, in which parenchymal plaque load starts at 2months of age. Transgenic 5xFAD mice show the first behavioral deficits at 6months, which are evident at 9months of age. In this study, we investigated the pharmacological influence of methylphenidate (MPH) on behavioral deficits of 5xFAD mice. Using a battery of behavioral tests, we observed no influence of MPH on anxiety in the elevated plus maze, whereas the locomotion and explorative activity in the open field was increased in transgenic and non-transgenic 5xFAD mice after the application of MPH. Further MPH inhibits habituation in the open field in healthy 5xFAD littermates after the application of 10mg/kg MPH. On the other hand, 10mg/kg MPH improved spatial memory in 6-month-old transgenic 5xFAD males, i.e., at a time point when deficits start to occur. However, in 9-month-old transgenic mice, MPH did not improve persisting learning and memory deficits. We concluded that MPH might improve the non-cognitive, apathy-like behavior (indicated by a reduced exploration), but it has no influence on sustained Alzheimer typical learning and memory deficits.
KW  - Alzheimer Disease: drug therapy
KW  - Alzheimer Disease: genetics
KW  - Alzheimer Disease: psychology
KW  - Amyloid beta-Protein Precursor: genetics
KW  - Animals
KW  - Anxiety: drug therapy
KW  - Behavior, Animal: drug effects
KW  - Behavior, Animal: physiology
KW  - Central Nervous System Stimulants: pharmacology
KW  - Disease Models, Animal
KW  - Exploratory Behavior: drug effects
KW  - Habituation, Psychophysiologic: drug effects
KW  - Humans
KW  - Male
KW  - Maze Learning: drug effects
KW  - Methylphenidate: pharmacology
KW  - Mice
KW  - Mice, Transgenic
KW  - Motor Activity: drug effects
KW  - Mutant Proteins: genetics
KW  - Presenilin-1: genetics
KW  - Amyloid beta-Protein Precursor (NLM Chemicals)
KW  - Central Nervous System Stimulants (NLM Chemicals)
KW  - Mutant Proteins (NLM Chemicals)
KW  - PSEN1 protein, human (NLM Chemicals)
KW  - Presenilin-1 (NLM Chemicals)
KW  - Methylphenidate (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25449360
DO  - DOI:10.1016/j.pbb.2014.11.006
UR  - https://pub.dzne.de/record/137747
ER  -