Jean Lud Cadet, M.D.
Molecular Neuropsychiatry Branch, Molecular Neuropsychiatry Section
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.
- Cadet JL, Brannock C, Krasnova IN, Jayanthi S, Ladenheim B, McCoy MT, Walther D, Godino A, Pirooznia M, Lee RS. Genome-wide DNA hydroxymethylation identifies potassium channels in the nucleus accumbens as discriminators of methamphetamine addiction and abstinence. Mol Psychiatry. 2017;22(8):1196-1204.
- Jayanthi S, Gonzalez B, McCoy MT, Ladenheim B, Bisagno V, Cadet JL. Methamphetamine Induces TET1- and TET3-Dependent DNA Hydroxymethylation of Crh and Avp Genes in the Rat Nucleus Accumbens. Mol Neurobiol. 2018;55(6):5154-5166.
- Krasnova IN, Gerra MC, Walther D, Jayanthi S, Ladenheim B, McCoy MT, Brannock C, Cadet JL. Compulsive methamphetamine taking in the presence of punishment is associated with increased oxytocin expression in the nucleus accumbens of rats. Sci Rep. 2017;7(1):8331.
- 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.
- Blackwood CA, Hoerle R, Leary M, Schroeder J, Job MO, McCoy MT, Ladenheim B, Jayanthi S, Cadet JL. Molecular Adaptations in the Rat Dorsal Striatum and Hippocampus Following Abstinence-Induced Incubation of Drug Seeking After Escalated Oxycodone Self-Administration. Mol Neurobiol. 2019;56(5):3603-3615.
Related Scientific Focus Areas
Genetics and Genomics
Molecular Biology and Biochemistry
This page was last updated on Friday, November 2, 2018