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Androgen modulation of behavioural flexibility in male rats Lo, Valerie

Abstract

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.

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Attribution-NonCommercial-NoDerivatives 4.0 International