Compulsive methamphetamine taking induces autophagic and apoptotic markers in the rat dorsal striatum.

Archives of Toxicology
Rajeev SubuJ L Cadet

Abstract

Methamphetamine (METH) use disorder (MUD) is often accompanied by psychotic symptoms, cognitive deficits, and pathological changes in the brains of users. Animals that experimenters injected with drugs also show neurodegenerative changes in their brains. Recently, we have been investigating METH-induced molecular and biochemical consequences in animals that had infused themselves with METH using the drug self-administration (SA) paradigm. In that model, footshocks administered contingently help to separate rats that had already escalated their METH intake into resilient-to-drug (shock-sensitive, SS) or compulsive (shock-resistant, SR) METH takers. Herein, we used that model to test the idea that compulsive METH takers might show evidence of drug-induced autophagic changes in their brains. There were significant increases in mRNA levels of autophagy-related genes including Atg2a, Atg5, Atg14, and Atg16L1 in the rat dorsal striatum. Levels of two autophagy biomarkers, autophagy activating kinase (ULK1) and phospho-Beclin1, were also increased. In addition, we found increased p53 but decreased Bcl-2 protein levels. Moreover, the expression of cleaved initiator caspase-9 and effector caspase-6 was higher in compulsive METH takers i...Continue Reading

References

Apr 1, 1981·Pharmacology, Biochemistry, and Behavior·S E BittnerL S Seiden
May 23, 1998·Neurochemistry International·J L Cadet, C Brannock
Jul 18, 2001·Brain Research. Molecular Brain Research·S Z ImamS F Ali
Aug 2, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·S JayanthiJ L Cadet
Feb 8, 2002·Journal of Addictive Diseases·Arthur K Cho, William P Melega
Oct 2, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jean Lud CadetXiaolin Deng
Feb 11, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Subramaniam JayanthiJean Lud Cadet
Jan 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Subramaniam JayanthiJean Lud Cadet
Sep 24, 2005·Cell·Sophie PattingreBeth Levine
Dec 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Amir A LevineJames H Schwartz
Jan 4, 2006·Archives of General Psychiatry·Yoshimoto SekineNorio Mori
Dec 29, 2006·The Journal of Biological Chemistry·Minako MatsushitaFuyuhiko Inagaki
Apr 24, 2007·Neurotoxicity Research·Jean Lud CadetJohnalyn Lyles
Aug 25, 2007·Nature Reviews. Molecular Cell Biology·M Chiara MaiuriGuido Kroemer
Oct 12, 2007·Biochimie·Sophie PattingrePatrice Codogno
Jan 15, 2008·Cell·Beth Levine, Guido Kroemer
May 21, 2008·Journal of Neurochemistry·Roberta CastinoCiro Isidoro
Nov 11, 2008·Annals of the New York Academy of Sciences·Livia PasqualiFrancesco Fornai
Mar 31, 2009·Brain Research Reviews·Irina N Krasnova, Jean Lud Cadet
Sep 25, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Bernard W Balleine, John P O'Doherty
Dec 23, 2009·Substance Use & Misuse·W Susan ChengThomas L Patterson
Feb 8, 2011·Neurobiology of Disease·Ralph A Nixon, Dun-Sheng Yang
Dec 4, 2012·Nature Structural & Molecular Biology·Chinatsu OtomoTakanori Otomo
Dec 3, 2013·Acta Neuropathologica·Jean Lud CadetChristopher Mark Milroy
Mar 4, 2014·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Irina N KrasnovaJean L Cadet
Oct 7, 2014·International Journal of Biological Sciences·Haijian WuYuan Hong
Dec 20, 2014·Cell Death and Differentiation·S ShaliniS Kumar
Jan 16, 2015·Neurotoxicity Research·Rujiraporn PitaksaleePimtip Sanvarinda
Apr 3, 2015·The Journal of Biological Chemistry·Katy J PetherickIan G Ganley
Apr 10, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·F Javier RubioBruce T Hope
Aug 9, 2015·Annual Review of Psychology·Barry J Everitt, Trevor W Robbins
Sep 24, 2015·Cellular and Molecular Life Sciences : CMLS·Sebastian Wesselborg, Björn Stork

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Citations

Jan 31, 2021·International Journal of Molecular Sciences·Michael T McCoyJean Lud Cadet
Jun 30, 2021·Experimental Neurology·Subramaniam JayanthiJean Lud Cadet

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Methods Mentioned

BETA
PCR

Software Mentioned

StatView
LightCycler probe design
GraphPad Prism
Image Lab

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