Behavioral, cognitive, and safety profile of 2-deoxy-2-glucose (2DG) in adult rats

2-Deoxy-D-glucose (2DG), a glucose analog that transiently inhibits glycolysis, has anticonvulsant and antiepileptic disease-modifying properties in experimental in vivo models of seizures and epilepsy. Here we evaluated the effects of 2DG across the range of doses (50-500mg/kg i.p.) shown previously to exert anticonvulsant and antiepileptic effects in rats, on spatial learning and memory using the Morris water maze and on exploratory behavior using the open field test. For water maze testing, both acute and chronic protocols were tested. For acute testing, 2DG was injected for 15min prior to the water maze trial only on testing days. For chronic testing, 2DG was injected daily for 14days before water maze testing began. Neither protocol altered the latency to platform acquisition or retention of platform location by the probe test. For open field testing, 2DG was given at doses of 50-250mg/kg 15 or 30min prior to testing on each testing day. When given 30min prior to testing, exploratory activity in the open field was transiently and reversibly decreased by 2DG at doses of 250mg/kg/day but there were no effects on open field activity at 50mg/kg/day. When given 15min prior to testing, 2DG decreased exploratory activity in a dose-dependent fashion at both 50 and 250mg/kg. There were no toxic effects of 2DG at doses of 500mg/kg/day on body weight or general health. In summary, 2DG is well tolerated at doses associated with anticonvulsant and antiepileptic effects, supporting its potential as an anticonvulsant and antiepileptic agent with a novel mechanism of action.