Impact of impaired glucose metabolism on responses to a psychophysical stressor: modulation by ketamine.

Rationale: There is evidence that hypoglycemia, a metabolic stressor, can negatively impact mood and motivation, and can interact with other stressors to potentiate their effects on behavior and physiology.

Objectives/methods: The current study in male Sprague-Dawley rats explored the interaction between impaired glucose metabolism induced by 0, 200, or 300 mg/kg 2-deoxy-D-glucose (2-DG) and a psychophysical stressor induced by forced swimming stress (FSS; 6 sessions, 10 min/session). The endpoints of interest were blood glucose levels, progressive behavioral immobility, and saccharin preference (2-bottle choice test). Furthermore, it was investigated whether pre-treatment with 0, 10, or 20 mg/kg ketamine could modify the interaction between 2-DG and FSS on these endpoints.

Results: It was found that 2-DG increased blood glucose levels equally in all experimental groups, accelerated the immobile response to FSS, and suppressed saccharin preference 1 week following termination of stress exposure. As well, pre-treatment with ketamine blocked the effects of combined 2-DG and FSS on immobility and saccharin preference without affecting blood glucose levels and produced an anti-immobility effect that was observed during a drug-free test swim 1 week following administration.

Conclusions: Overall, these findings demonstrate that impaired glucose metabolism can potentiate the effects of a psychophysical stressor, and that this interaction can be modulated pharmacologically by ketamine.