The research in Dr. Cadet’s section focuses on studies of the molecular and cellular mechanisms of psychostimulant addiction and toxicity. Dr. Cadet’s group has provided recent evidence that methamphetamine (METH) self-administration is accompanied with markers of toxicity in striatal dopaminergic systems. These results are consistent with the idea that catecholamines, especially, dopamine can activate neurodegenerative processes in the mammalian brain. They have also shown recently that METH preconditioning protects against METH toxicity. This occurs by upregulation of neurotrophic factors such as BDNF and/or downregulation of glutamatergic systems. Preliminary studies have shown that these changes are secondary to epigenetic modifications that include histone hypoacetylation and DNA methylation. The laboratory is thus pursuing investigations to further identify epigenetic markers that are involved in METH self-administration and METH preconditioning.