An Exploration of the Aversive Properties of 2-deoxy-D-glucose in the Context of Metabolic Dysfunction and Mood Disorders

Horman, Thomas
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University of Guelph

There is evidence that hypoglycemia alters mood and induces depressive-like behaviours. One method to precipitate a state of acute hypoglycemia is to administer the glucose antimetabolite 2-deoxy-D-glucose (2-DG). This thesis explored whether 2-DG could produce a conditioned place avoidance (CPA) in rats and examined whether pharmacological manipulation of monoamines could alter this effect. Pre-fed rats avoided a compartment paired with 2-DG (300 or 500 mg/kg). 2-DG also increased blood glucose and corticosterone (CORT), and suppressed locomotor activity. Interestingly food deprivation eliminated 2-DG-induced CPA, despite enhancing blood glucose and CORT levels. Clonidine (10 and 40 ug/kg) and bupropion (10 and 30 mg/kg) attenuated 2-DG-induced CPA and reduced increases in blood CORT caused by 2-DG, while bupropion reversed locomotor deficits. Overall, these results suggest that acute impairment of glucose metabolism can elicit a stress response which is aversive to rats, and which involves neurochemical mechanism of stress, arousal, and mood.

Place avoidance, 2 deoxy-D-glucose, corticosterone, blood glucose, clonidine, bupropion