Evaluation of an Aβ1–40-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 Aβ1–40 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 Aβ1–40-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 Aβ1–40 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 Aβ1–40 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 Aβ1–40 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 Aβ1–40 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.

► Our laboratory is the first to utilize a reward-directed instrumental learning procedure in a dementia study.
► Aβ1–40 injection affects the acquisition of the lever-pressing response rather than its maintenance.
► Aβ1–40 injection impairs the ability to adjust behavior to adapt to action–outcome contingency changes.
► Aβ1–40 injection impairs the ability to make a stimulus–response association from a two-color visual stimulus.
► This series of instrumental learning tasks has the potential to be applied in dementia research as a new cognitive behavior testing method.