Chronic administration of heroin to mice produces up-regulation of brain apoptosis-related proteins and impairs spatial learning and memory

Neuropharmacology
Mónica TramullasMaría A Hurlé

Abstract

Several studies open up the possibility that chronic exposure to opioid drugs in the CNS would interfere with learning and memory through a neurotoxic effect related to activation of apoptotic pathways. Here, we have analyzed the effects of prolonged heroin administration on sensorimotor and cognitive performance in mice, as well as the associated changes in brain expression of proteins regulating the extrinsic (FasL and Fas) and the mitochondrial (Bcl-2, Bcl-X(L), Bad and Bax) apoptotic pathways. Our findings indicate that chronic heroin did not interfere with mice performance in a battery of sensorimotor tests. On the other hand, cognitive ability in the Morris water maze and cognitive flexibility-related performance were strongly impaired by chronic heroin. These effects were associated with up-regulation of pro-apoptotic proteins such as Fas, FasL and Bad, in the cortex and hippocampus, indicating the activation of both the death receptor and the mitochondrial apoptotic pathways. Another indicator of apoptosis was the presence of TUNEL (TdT-mediated dUTP nick-end labeling) positive cells scattered throughout the brain.

References

Jun 1, 1979·Pharmacology, Biochemistry, and Behavior·I S ZagonC I Thompson
Feb 1, 1975·Archives of General Psychiatry·E R GritzJ Schlesinger
Jan 1, 1991·Psychopharmacology·J W Spain, G C Newsom
Dec 1, 1990·Behavioral Neuroscience·B S Givens, D S Olton
Nov 30, 1987·Drug and Alcohol Dependence·D GuerraA Tobeña
Jan 1, 1985·Journal of Substance Abuse Treatment·L Miller
Jun 24, 1982·Nature·R G MorrisJ O'Keefe
Jul 9, 1998·Neuroscience Letters·R M EscorihuelaA Fernández-Teruel
Feb 4, 1999·Nature·D YinY Shi
Apr 18, 2000·Human Molecular Genetics·L M Tarantino, M Bucan
Apr 19, 2000·The Journal of Experimental Medicine·D YinY Shi
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·A J EischE J Nestler
Jul 8, 2000·Addiction·S DarkeW Wickes
Aug 23, 2001·Brain Research. Brain Research Reviews·R D'Hooge, P P De Deyn
Aug 23, 2001·Forensic Science International : Synergy·C Brehmer, P X Iten
Dec 26, 2001·Pharmacology & Therapeutics·K C ZimmermannD R Green
Apr 9, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Pravin C SinghalAditi A Kapasi
Jun 14, 2002·Drug and Alcohol Dependence·Miriam Z Mintzer, Maxine L Stitzer
Jan 1, 1990·The European Journal of Neuroscience·R. G. M. MorrisL. E. Jarrard
Aug 15, 2002·Physiology & Behavior·Ilana J HepnerAlan J Taylor
Sep 5, 2002·Nature Reviews. Cancer·Suzanne Cory, Jerry M Adams
Sep 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jinghua WangSabita Roy
Mar 12, 2003·Addictive Behaviors·Michael Lyvers, Michael Yakimoff
May 14, 2003·Behavioural Brain Research·Hennariikka IivonenJukka Puoliväli
Oct 8, 2003·Naunyn-Schmiedeberg's Archives of Pharmacology·M Julia García-FusterJesús A García-Sevilla
Jun 11, 2004·Annual Review of Biochemistry·Xuejun Jiang, Xiaodong Wang
Aug 18, 2004·Behavioural Brain Research·Cédrick Florian, Pascal Roullet
Oct 7, 2004·Neuropharmacology·Terry E Robinson, Bryan Kolb
Dec 22, 2004·Progress in Neuro-psychopharmacology & Biological Psychiatry·Charalabos C PapageorgiouAndreas D Rabavilas
Apr 23, 2005·Drug and Alcohol Dependence·Miriam Z MintzerMaxine L Stitzer
May 11, 2005·Proceedings of the National Academy of Sciences of the United States of America·Nicolas P RougierRandall C O'Reilly
May 17, 2005·Drug and Alcohol Dependence·Antonio VerdejoMiguel Pérez-García
Sep 15, 2005·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Karen D ErscheBarbara J Sahakian

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Citations

Jan 20, 2012·Psychopharmacology·Erin CumminsFrancesco Leri
Aug 7, 2012·Journal of Molecular Neuroscience : MN·Shiva Nasiraei-MoghadamLeila Dargahi
Oct 6, 2011·Nature Reviews. Neuroscience·Aldo BadianiYavin Shaham
Mar 15, 2012·Neuroscience Research·Anna KubesovaJiri Horacek
Feb 8, 2011·Pharmacology, Biochemistry, and Behavior·Bríd Áine Nic Dhonnchadha, Kathleen M Kantak
Mar 5, 2016·Frontiers in Psychiatry·Jarid Goodman, Mark G Packard
Oct 14, 2009·Medical Hypotheses·Wang YingHan Tai-Zhen
Oct 2, 2009·Peptides·Richard J Bodnar
Apr 29, 2008·Brain Research Reviews·Teresa Cunha-OliveiraCatarina R Oliveira
Mar 14, 2008·Behavioural Brain Research·Mónica TramullasMaría A Hurlé
May 3, 2011·Pain·Jarred W YoungerSean C Mackey
Nov 22, 2014·Psychopharmacology·Gerusa Paz PortoCarlos Fernando Mello
Sep 14, 2012·Journal of Applied Toxicology : JAT·María José PolancoCarmen González-Martín
Jan 22, 2020·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Mi Ran ChoiDai-Jin Kim
Dec 7, 2018·Nature Reviews. Neuroscience·Cherkaouia KibalyPing-Yee Law
Nov 13, 2020·Pediatric Research·Stephanie L MerharNehal A Parikh

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