Jean Lud Cadet, M.D.
Molecular Neuropsychiatry Research Branch
251 Bayview Boulevard
Baltimore MD 21224
Research in our section focuses on studies 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. We 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.
Jayanthi S, Deng X, Ladenheim B, McCoy MT, Cluster A, Cai NS, Cadet JL. Calcineurin/NFAT-induced up-regulation of the Fas ligand/Fas death pathway is involved in methamphetamine-induced neuronal apoptosis. Proc Natl Acad Sci U S A. 2005;102(3):868-73.
Krasnova IN, Marchant NJ, Ladenheim B, McCoy MT, Panlilio LV, Bossert JM, Shaham Y, Cadet JL. Incubation of methamphetamine and palatable food craving after punishment-induced abstinence. Neuropsychopharmacology. 2014;39(8):2008-16.
Sekine Y, Ouchi Y, Sugihara G, Takei N, Yoshikawa E, Nakamura K, Iwata Y, Tsuchiya KJ, Suda S, Suzuki K, Kawai M, Takebayashi K, Yamamoto S, Matsuzaki H, Ueki T, Mori N, Gold MS, Cadet JL. Methamphetamine causes microglial activation in the brains of human abusers. J Neurosci. 2008;28(22):5756-61.
Cadet JL, Brannock C, Jayanthi S, Krasnova IN. Transcriptional and epigenetic substrates of methamphetamine addiction and withdrawal: evidence from a long-access self-administration model in the rat. Mol Neurobiol. 2015;51(2):696-717.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on July 17th, 2017