Chapter 90 - Testosterone and Striatal Dopaminergic Neurotoxicity

Abstract

Testosterone (T) enhances the degree of neurotoxicity when present prior to the administration of neurotoxins that target the nigrostriatal dopaminergic (NSDA) system, but does so only for NSDA neurotoxicity induced by the psychostimulant methamphetamine (MA). No such effect was observed on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, and in response to 6-hydroxydopamine it appears that the increased neurotoxicity obtained in intact versus orchidectomized rats is due to estrogen produced by aromatization of T. Some mechanisms through which T may enhance striatal neurotoxicity include effects upon transporters, both dopamine transporters and vesicular monoamine transporter-2; heat-shock proteins; hyperthermia; and infarcts. In addition, generalized effects of T upon apoptosis and necrosis may contribute to striatal neurotoxicity. Some notable inferences of these findings include the potential damage to NSDA function with the combination of T and MA as can occur in athletes striving to augment their performance. In addition, endogenously elevated T levels that accompany training and/or result from exogenous supplements may increase brain damage resulting from trauma (e.g., MA, concussions).