Androgen modulation of behavioural flexibility in male rats

Behavioural flexibility, the ability to adapt behaviour in response to environmental changes, is regulated by the mesocorticolimbic system. Strategy set-shifting is one form of behavioural flexibility, where subjects initially learn one rule to receive a reward (e.g., select the lever illuminated by a visual-cue, or the “light rule”), but then must switch to a novel rule (e.g., select the lever in one position, regardless of visual-cue, or the “side rule”). Androgens, such as testosterone (T), are produced locally within the mesocorticolimbic system, and T treatment impairs set-shifting. Decreasing androgens with the androgen synthesis inhibitor abiraterone acetate (ABI) improves performance of male rats on the strategy set-shifting task using the light-side shift. However, the effect of ABI treatment was small. In this study, we assess different set-shifting procedures to make the strategy set-shifting task more difficult and examine whether this may increase the effect size of ABI treatment. In the first study, rats were assigned to one of six different set-shifting tasks, which required them to perform either the light-side shift or side-light shift, with variable numbers of minimum learning trials for the initial discrimination and with or without 20 reminder trials prior to the set-shift. The side-light shift was significantly more difficult than the light-side shift, as indicated by rats making a greater number of errors to criterion, perseverative errors, regressive errors, and never-reinforced errors on the set-shift and requiring a greater number of trials to criterion to complete the task. In the second study, rats were assigned to (1) ABI or vehicle treatment and (2) the light-side or side-light shift. We replicated our previous findings showing that the side-light shift was significantly more difficult. However, we found no effect of ABI on either type of shifts. These data demonstrate one version of the strategy set-shifting task that is more difficult and provide more insight into the potential role of androgens in behavioural flexibility in male rats.Arts, Faculty ofPsychology, Department ofGraduat