Effect of donepezil on reversal learning in a touch screen-based operant task

Area of Science:

• Neuroscience
• Behavioral Science
• Pharmacology

Background:

• Reversal learning impairments are common in psychiatric disorders and difficult to treat.
• The efficacy of cholinergic enhancers in improving behavioral flexibility is debated.
• Acetylcholinesterase inhibitors are a class of drugs that enhance cholinergic neurotransmission.

Purpose of the Study:

• To investigate the effect of donepezil, an acetylcholinesterase inhibitor, on Probabilistic Reversal Learning (PRL) performance in healthy rats.
• To determine if donepezil can enhance behavioral flexibility in a rodent model.
• To explore the therapeutic potential of central acetylcholinesterase inhibition for behavioral inflexibility.

Main Methods:

• Lister-Hooded rats were trained on an automated touchscreen operant task involving discrimination of two stimuli for food rewards.
• After achieving steady performance, the stimulus-reward rule was reversed.
• Donepezil was administered systemically 30 minutes prior to daily 30-minute training sessions for 24 days.

Main Results:

• Systemic donepezil treatment did not affect trial accuracy during the initial two-stimulus discrimination training phase.
• Rats treated with donepezil demonstrated significantly enhanced performance during the reversal learning phase.
• The results indicate that donepezil improved the ability to adapt to a changing stimulus-reward contingency.

Conclusions:

• Donepezil significantly enhanced Probabilistic Reversal Learning performance in healthy animals.
• Inhibition of central acetylcholinesterase appears to be a promising therapeutic strategy for addressing behavioral inflexibility.
• These findings suggest that cholinergic enhancement may be a viable approach for treating cognitive deficits associated with psychiatric disorders.