Cognitive ability declines with age, ranging from normal age-related decline to mild cognitive impairment and to dementias like Alzheimer's disease. One domain which is particularly affected is executive function. Attentional set-shifting and reversal learning tasks have been widely used to quantify executive dysfunction in older humans and rats. Here, we describe the establishment of an operant conditioning task to assess reversal learning in rats. We investigated a series of pharmacological interventions, including drugs affecting cholinergic and serotonergic transmission, previously shown to have pro-cognitive effects in animal models and humans. The reversal learning task utilises a rule learning (non-match response) protocol with a reversal (match response) component. After a week’s habituation to the operant chambers and the task, male Sprague Dawley rats (n= 10 per group) were trained to a criteria of above 90% correct on the non-match response (approximately 10 days). Following reversal of the correct response to the match response, rats received daily drug administration prior to the task. The reversal learning phase of the task continued until rats again achieved criteria (90% correct response). A number of compounds have been assessed in this reversal paradigm. Pro-cognitive effects have been observed both using nicotine (acetylcholine receptor agonist; P<0.05 on sessions 5-8 of reversal compared to control) and SB-399885 (5-HT6 antagonist; P<0.05 on session 7 of reversal compared to control). A breakdown of test sessions into smaller trial bins has yielded a better temporal resolution of the data to assess changes within as well as between testing sessions. These data demonstrate the successful establishment of an operant reversal learning task in rats. The task is sensitive to pharmacological intervention and therefore can be used to investigate the potential pro-cognitive effects of drugs under development for treatment of cognitive dysfunction associated with psychiatric and neurodegenerative disease. Future studies in aged animals and disease models will explore the possibility of employing the task to assess disease specific deficits in executive functioning.