An exploration of the aversive properties of 2-deoxy-D-glucose in rats.

Abstract

Hypoglycemia can alter arousal and negatively impactmood. This study tests the hypothesis that acute drops in glucose metabolism cause an aversive state mediated by monoamine activity. In experiment 1, male Sprague-Dawley rats were either food deprived (FD) or pre-fed (PF) and tested on conditioned place avoidance (CPA; biased place conditioning design; 3 pairings drug/vehicle, each 30min-long) induced by the glucose antimetabolite 2-deoxy-D-glucose (2-DG; 0, 300 or 500mg/kg, SC). Locomotion and blood glucose were also assessed. Experiment 2 examined whether clonidine (noradrenergic α2 agonist, 0, 10 or 40μg/kg, SC) or bupropion (monoamine reuptake blocker, 0, 10 or 30mg/kg, SC) could alter CPA induced by 500mg/kg 2-DG. In experiment 3, blood corticosterone (CORT) was measured in response to 500mg/kg 2-DG, alone or in combination with 40μg/kg clonidine or 30mg/kg bupropion. Finally, experiment 4 controlled for possible place conditioning induced by 10 or 40μg/kg clonidine, or 10 or 30mg/kg bupropion injected without 2-DG. It was found that 2-DG increased blood glucose and produced a robust CPA. The feeding status of the animals modulated these effects, including CORT levels. Both clonidine and bupropion attenuated the effects of 2-DG on CPA and CORT, but only bupropion reversed suppression of locomotion. Taken together, these results in rats suggest that impaired glucose metabolism can negatively impact arousal and mood via effects on HPA and monoamine systems.