Histone deacetylase inhibitor sodium butyrate increases risk-taking during acquisition of the rat gambling task.

rationalePairing casino-inspired audiovisual cues with reward delivery significantly increases risky decision-making in laboratory-based gambling tasks across rats and humans. The neurocognitive mechanisms underlying this effect are unclear. Data from the rat gambling task (rGT) suggests win-paired cues render choice insensitive to reinforcer devaluation, indicating habitual control of decision-making. Histone deacetylase enzymes (HDACs) negatively mediate gene expression. Inhibiting this process can facilitate the formation of long-term memories and accelerate habit formation.

objectiveWe therefore hypothesised that risky decision making in the cued rGT could be enhanced by administration of the non-specific class I HDAC inhibitor sodium butyrate (NaBut).

methodsMale Long Evans rats received NaBut after each cued rGT session during task acquisition.

resultsNaBut-treated rats developed a bias towards the risky options more rapidly during the first five training sessions. Immunohistochemical analysis indicated a relative increase in histone acetylation in the striatum and prelimbic frontal cortex after five days of NaBut treatment. Modeling the data using previously established reinforcement learning algorithms optimised for the rGT suggests that NaBut concurrently increased learning from rewards while also decreasing learning from punishments during this early learning period. However, once training was complete, NaBut-treated animals were just as sensitive as controls to the omission of reward, although behavioural changes were less apparent in risk-preferring rats.

conclusionsThese findings suggest that development of a maladaptive, risky strategy while learning the cued rGT can be facilitated through HDAC inhibition, but fall short of conclusively demonstrating that such treatment results in greater habitual control over behaviour.