Evaluation of an Aβ(1-40)-induced cognitive deficit in rat using a reward-directed instrumental learning task.
Alzheimer's disease (AD) is the most common form of dementia. It is a progressive neurodegenerative disorder that leads to gradual loss of cognitive and functional abilities, and development of behavioral disturbances. Previous studies using Aβ(1-40) microinjection in animal models focused on cognitive deficits in spatial learning and avoidance conditioning. However, no attempt has been made to determine the sensitivity of an Aβ(1-40)-manipulated animal model in tasks involving reward-directed instrumental learning (RDIL). Thus, the present study was designed to investigate the effects of intra hippocampal microinjection of Aβ(1-40) on the acquisition and maintenance of a basic instrumental response (lever-pressing), then on the goal directed (higher response ratio) and habit (visual signal discrimination and extinction) learning, as well as on neurotransmitter changes which could potentially alter the regulatory processes involved in instrumental learning. Our present findings demonstrated that the focal hippocampal microinjection of Aβ(1-40) rendered rats unable to process new cue/contextual information in the formation of causal relation, rather than affecting the operant action itself. Although the injected Aβ(1-40) did not directly influence performance, it did prevent the information from being translated into action. Moreover, the neurotransmitter results indicated that multiple neural signaling might be involved in the regulation of RDIL in the Aβ(1-40) injection model. In conclusion, results suggested that our series of instrumental learning tasks may have potential in dementia research as a novel method for testing cognitive behavior.
Research Center for Pharmacology & Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Zhe
Z
Shi
Xiuping
X
Sun
Xinmin
X
Liu
Shanguang
S
Chen
Qi
Q
Chang
Lingling
L
Chen
Guangqing
G
Song
Haiqing
H
Li
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004192:Discrimination, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012055:Reinforcement Schedule; D012201:Reward
D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)