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Food for thought: diet-induced impairments to decision-making and amelioration by N-acetylcysteine in male rats

Serena Becchi, Joshua Hood, Michael D. Kendig, Aida Mohammadkhani, Megan L. Shipman, Bernard W. Balleine, Stephanie L. Borgland & Laura H. Corbit

Psychopharmacology volume 239, pages3495–3506

October 2022


Attempts to lose weight often fail despite knowledge of the health risks associated with obesity and determined efforts. We previously showed that rodents fed an obesogenic diet displayed premature habitual behavioural control and weakened flexible decision-making based on the current value of outcomes produced by their behaviour. Thus, habitual control may contribute to failed attempts to modify eating behaviours.

To examine the effects of an obesogenic diet on behavioural control and glutamate transmission in dorsal striatum regions and to assess the ability of N-acetylcysteine (NAC) to reverse deficits.

Here, we examined diet-induced changes to decision-making and used in vitro electrophysiology to investigate the effects of diet on glutamate transmission within the dorsomedial (DMS) and dorsolateral (DLS) striatum, areas that control goal-directed and habitual behaviours, respectively. We administered NAC in order to normalize glutamate release and tested whether this would restore goal-directed performance following an obesogenic diet.

We found that an obesogenic diet reduced sensitivity to outcome devaluation and increased glutamate release in the DMS, but not DLS. Administration of NAC restored goal-directed control and normalized mEPSCs in the DMS. Finally, NAC administered directly to the DMS was sufficient to reinstate sensitivity to outcome devaluation following an obesogenic diet.

These data indicate that obesogenic diets alter neural activity in the basal ganglia circuit responsible for goal-directed learning and control which leads to premature habitual control. While the effects of diet are numerous and widespread, normalization of glutamatergic activity in this circuit is sufficient for restoring goal-directed behaviour.

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