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

Megan L Shipman,Laura H Corbit

doi:10.1038/s41398-022-01807-2

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.

Highlights

Obesity, and associated disease burden, is a preventable global health problem with over half of the adult population being classified as overweight or obese in 2016, equating to 1.9 billion people worldwide [1]
Furlong et al [4] showed that feeding rats a diet of sweetened condensed milk (SCM) for five weeks prior to instrumental training, where rats learned to press a lever for a different food reinforcer, resulted in insensitivity to the devaluation of that outcome following an amount of training where control subjects were sensitive to devaluation
Across days and that the SCM groups responded less than chow and to test our hypothesis that LY379268 would rescue a dietinduced impairment, we examined the effect of LY379268 on sensitivity to devaluation in each the Chow and SCM groups

Summary

Introduction

Associated disease burden, is a preventable global health problem with over half of the adult population being classified as overweight or obese in 2016, equating to 1.9 billion people worldwide [1]. These analyses and results from Experiment 1 suggest that overall, there and importantly, treatment with LY379268 improved sensitivity to is not a consistent sex difference or effect of diet on instrumental devaluation evidenced by a drug x devaluation interaction responding by the end of acquisition.

Results

Conclusion