EFFECTS OF 2-DEOXY-D-GLUCOSE ON METHAMPHETAMINE-INDUCED DOPAMINE AND SEROTONIN NEUROTOXICITY

The mechanisms underlying the neurotoxic actions of methamphetamine (M ETH) and related substituted amphetamines are unknown. Previous studie s with 2-deoxyglucose (2-DG) have suggested that METH-induced neurotox icity may involve exhaustion of intracellular energy stores. However, because 2-DG also produces hypothermic effects, and because METH's neu rotoxic actions are highly susceptible to thermoregulatory influence, previous findings with 2-DG are difficult to interpret. The present st udies were undertaken to further examine the influence of 2-DG's gluco privic and thermic effects in the context of METH-induced dopamine (DA ) and serotonin (5-HT) neurotoxicity. 2-DG protected against METH-indu ced DA neurotoxicity in both rats and mice. In both species, 2-DG, alo ne or in combination with METH, produced hypothermic effects. METH's t oxic effects on brain 5-HT neurons were either unaffected or exacerbat ed by 2-DG, depending on species, brain region, and dose of METH teste d. These results indicate that different mechanisms may underlie METH- induced DA and 5-HT neurotoxicity, and suggest that, as compared with 5-HT neurons, DA neurons are more susceptible to temperature influence , whereas 5-HT neurons are more vulnerable than DA neurons to metaboli c compromise. Additional studies are needed to further assess the role of energy stores in the neurotoxic effects of METH and related drugs.