Diet-induced deficits in goal-directed control are rescued by agonism of group II metabotropic glutamate receptors in the dorsomedial striatum

Abstract

Abstract Many overweight or obese people struggle to sustain the behavioural changes necessary to achieve and maintain weight loss. In rodents, obesogenic diet can disrupt goal-directed control of responding for food reinforcers, which may indicate that diet can disrupt brain regions associated with behavioural control. We investigated a potential glutamatergic mechanism to return goal-directed control to rats who had been given an obesogenic diet prior to operant training. We found that an obesogenic diet reduced goal-directed control and that systemic injection of LY379268, a Group II metabotropic glutamate receptor (mGluR2/3) agonist, returned goal-directed responding in these rats. Further, we found that direct infusion of LY379268 into the dorsomedial striatum, a region associated with goal-directed control, also restored goal-directed responding in the obesogenic-diet group. This indicates that one mechanism through which obesogenic diet disrupts goal-directed control is glutamatergic, and infusion of a mGluR2/3 agonist into the DMS is sufficient to ameliorate deficits in goal-directed control.