Kronik Psikiyatrik Hastalıklarda Nöron Plastisitesi
Özet
Bu metin, yetişkinlikte de devam eden ve beynin çevreye uyum sağlama, kendini yenileme yeteneğini ifade eden nöron plastisitesinin kronik psikiyatrik hastalıklar üzerindeki rolünü incelemektedir. Geçmişteki inanışların aksine nörogenez ve sinaptogenez gibi süreçlerin erişkin çağda da aktif olduğu ve bu mekanizmalardaki bozulmaların psikiyatrik hastalıkların patogenezinde kritik rol oynadığı belirtilmektedir. Duygudurum bozukluklarında, özellikle kronik stresin glukokortikoid seviyelerini artırarak hipokampus ve prefrontal kortekste atrofiye, amigdalada ise hipertrofiye yol açtığı ve BDNF salınımını azalttığı gösterilmiştir. Şizofreni gibi nörogelişimsel bozukluklarda ise erken dönem sinaptik formasyon anomalileri ve özellikle "reelin" proteini eksikliği ile ergenlik dönemindeki aşırı sinaptik budama mekanizmaları öne çıkmaktadır. Madde kullanım bozukluklarında, maddelerin hipokampustaki sinaptik plastisiteyi (LTP/LTD) ve öğrenme-hafıza süreçlerini manipüle ederek bağımlılığı sürdürdüğü aktarılmaktadır. Antidepresan, antipsikotik, lityum gibi psikofarmakolojik tedavilerin ve psikoterapinin, klinik etkilerini bu hatalı beyin devrelerini ve nöroplastisiteyi hücresel düzeyde yeniden yapılandırarak gösterdiği biyolojik çalışmalarla kanıtlanmıştır. Dolayısıyla, sinir sisteminin yaşam boyu değişime açık olması, psikiyatrik hastalıkların anlaşılması ve yeni tedavi yöntemlerinin geliştirilmesi açısından umut verici bir zemin sunmaktadır.
This text examines the role of neuronal plasticity, which refers to the brain's capacity to adapt to environmental changes and regenerate throughout adulthood, in chronic psychiatric disorders. Contrary to historical beliefs, processes such as neurogenesis and synaptogenesis remain active in adults, and impairments in these mechanisms play a critical role in the pathogenesis of neuropsychiatric diseases. In mood disorders, chronic stress increases glucocorticoid levels, leading to atrophy in the hippocampus and prefrontal cortex, hypertrophy in the amygdala, and a decrease in BDNF release. In neurodevelopmental disorders like schizophrenia, early-stage synaptic formation anomalies, specifically the deficiency of the "reelin" protein, and excessive synaptic pruning during adolescence are emphasized. Regarding substance use disorders, chronic use alters synaptic plasticity (LTP/LTD) and learning-memory processes in the hippocampus, thereby maintaining addiction. Biological studies demonstrate that psychofarmacological treatments—such as antidepressants, antipsychotics, and lithium—along with psychotherapy exert their clinical efficacy by restructuring these faulty brain circuits and enhancing neuroplasticity at the microcellular level. Consequently, the lifelong adaptability of the nervous system provides a promising foundation for understanding mental illnesses and developing novel therapeutic methods.
Referanslar
Sadock BJ, Sadock VA, Ruiz P. Kaplan&Sadock’s Synopsis of Psychiatry Behavioral Sciences/Clinical Psychiatry. Wolters Kluwer/Lippincott Williams&Wilkins; 2015.
Calabrese F, Molteni R, Racagni G, et al. Neuronal plasticity: a link between stress and mood disorders. Psychoneuroendocrinology. Psychoneuroendocrinology; 2009;34 Suppl 1(SUPPL. 1). doi:10.1016/J.PSYNEUEN.2009.05.014
Öztürk MO, Uluşahin A. Ruh Sağlığı ve Bozuklukları. Ankara: BAYT Ltd. Şti.; 2015.
Kavalali ET, Monteggia LM. Targeting Homeostatic Synaptic Plasticity for Treatment of Mood Disorders. Neuron. Neuron; 2020;106(5): 715–726. doi:10.1016/J.NEURON.2020.05.015
Nanou E, Catterall WA. Calcium Channels, Synaptic Plasticity, and Neuropsychiatric Disease. Neuron. Neuron; 2018;98(3): 466–481. doi:10.1016/J.NEURON.2018.03.017
Bauer ME, Teixeira AL. Inflammation in psychiatric disorders: what comes first? Annals of the New York Academy of Sciences. Ann N Y Acad Sci; 2019;1437(1): 57–67. doi:10.1111/NYAS.13712
Baum AE, Akula N, Cabanero M, et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Molecular psychiatry. Mol Psychiatry; 2008;13(2): 197–207. doi:10.1038/SJ.MP.4002012
Heim C, Newport DJ, Heit S, et al. Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. JAMA. JAMA; 2000;284(5): 592–597. doi:10.1001/JAMA.284.5.592
Liu W, Ge T, Leng Y, et al. The Role of Neural Plasticity in Depression: From Hippocampus to Prefrontal Cortex. Neural plasticity. Neural Plast; 2017;2017. doi:10.1155/2017/6871089
Mayberg HS, Liotti M, Brannan SK, et al. Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. The American journal of psychiatry. Am J Psychiatry; 1999;156(5): 245–253. doi:10.1176/AJP.156.5.675
Koenigs M, Grafman J. The functional neuroanatomy of depression: Distinct roles for ventromedial and dorsolateral prefrontal cortex. Behavioural Brain Research. Elsevier; 2009;201(2): 239–243. doi:10.1016/J.BBR.2009.03.004
Marsden WN. Synaptic plasticity in depression: molecular, cellular and functional correlates. Progress in neuro-psychopharmacology & biological psychiatry. Prog Neuropsychopharmacol Biol Psychiatry; 2013;43: 168–184. doi:10.1016/J.PNPBP.2012.12.012
Bramham CR, Messaoudi E. BDNF function in adult synaptic plasticity: the synaptic consolidation hypothesis. Progress in neurobiology. Prog Neurobiol; 2005;76(2): 99–125. doi:10.1016/J.PNEUROBIO.2005.06.003
Dwivedi Y, Rizavi HS, Conley RR, et al. Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Archives of general psychiatry. Arch Gen Psychiatry; 2003;60(8): 804–815. doi:10.1001/ARCHPSYC.60.8.804
Pittenger C, Duman RS. Stress, depression, and neuroplasticity: a convergence of mechanisms. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Neuropsychopharmacology; 2008;33(1): 88–109. doi:10.1038/SJ.NPP.1301574
Sen S, Duman R, Sanacora G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biological psychiatry. Biol Psychiatry; 2008;64(6): 527–532. doi:10.1016/J.BIOPSYCH.2008.05.005
Bocchio-Chiavetto L, Zanardini R, Bortolomasi M, et al. Electroconvulsive Therapy (ECT) increases serum Brain Derived Neurotrophic Factor (BDNF) in drug resistant depressed patients. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. Eur Neuropsychopharmacol; 2006;16(8): 620–624. doi:10.1016/J.EURONEURO.2006.04.010
Hashimoto R, Senatorov V, Kanai H, et al. Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience. Elsevier Ltd; 2003;117(1): 55–61. doi:10.1016/S0306-4522(02)00577-8
Son H, Yu IT, Hwang SJ, et al. Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus. Journal of neurochemistry. J Neurochem; 2003;85(4): 872–881. doi:10.1046/J.1471-4159.2003.01725.X
Hao Y, Creson T, Zhang L, et al. Mood stabilizer valproate promotes ERK pathway-dependent cortical neuronal growth and neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience. J Neurosci; 2004;24(29): 6590–6599. doi:10.1523/JNEUROSCI.5747-03.2004
Paquette V, Lévesque J, Mensour B, et al. ‘Change the mind and you change the brain’: Effects of cognitive-behavioral therapy on the neural correlates of spider phobia. NeuroImage. Academic Press Inc.; 2003;18(2): 401–409. doi:10.1016/S1053-8119(02)00030-7
Price RB, Duman R. Neuroplasticity in cognitive and psychological mechanisms of depression: an integrative model. Molecular psychiatry. Mol Psychiatry; 2020;25(3): 530–543. doi:10.1038/S41380-019-0615-X
Falconer DS. Two new mutants, ‘trembler’ and ‘reeler’, with neurological actions in the house mouse (Mus musculus L.). Journal of genetics. J Genet; 1951;50(2): 192–205. doi:10.1007/BF02996215
Hamburgh M. ANALYSIS OF THE POSTNATAL DEVELOPMENTAL EFFECTS OF ‘REELER,’ A NEUROLOGICAL MUTATION IN MICE. A STUDY IN DEVELOPMENTAL GENETICS. Developmental biology. Dev Biol; 1963;8(2): 165–185. doi:10.1016/0012-1606(63)90040-X
Caviness VS, So DK, Sidman RL. The hybrid reeler mouse. The Journal of heredity. J Hered; 1972;63(5): 241–246. doi:10.1093/OXFORDJOURNALS.JHERED.A108286
D’Arcangelo G, Miao GG, Chen SC, et al. A protein related to extracellular matrix proteins deleted in the mouse mutant reeler. Nature. Nature; 1995;374(6524): 719–723. doi:10.1038/374719A0
Rice DS, Nusinowitz S, Azimi AM, et al. The reelin pathway modulates the structure and function of retinal synaptic circuitry. Neuron. Neuron; 2001;31(6): 929–941. doi:10.1016/S0896-6273(01)00436-6
Yip JW, Yip YPL, Nakajima K, et al. Reelin controls position of autonomic neurons in the spinal cord. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A; 2000;97(15): 8612–8616. doi:10.1073/PNAS.150040497
Phelps PE, Rich R, Dupuy-Davies S, et al. Evidence for a cell-specific action of Reelin in the spinal cord. Developmental Biology. Academic Press Inc.; 2002;244(1): 180–198. doi:10.1006/dbio.2002.0580
Boyle MP, Bernard A, Thompson CL, et al. Cell-type-specific consequences of Reelin deficiency in the mouse neocortex, hippocampus, and amygdala. The Journal of comparative neurology. J Comp Neurol; 2011;519(11): 2061–2089. doi:10.1002/CNE.22655
Anstötz M, Cosgrove KE, Hack I, et al. Morphology, input-output relations and synaptic connectivity of Cajal-Retzius cells in layer 1 of the developing neocortex of CXCR4-EGFP mice. Brain structure & function. Brain Struct Funct; 2014;219(6): 2119–2139. doi:10.1007/S00429-013-0627-2
Alcántara S, Ruiz M, D’Arcangelo G, et al. Regional and cellular patterns of reelin mRNA expression in the forebrain of the developing and adult mouse. The Journal of neuroscience : the official journal of the Society for Neuroscience. J Neurosci; 1998;18(19): 7779–7799. doi:10.1523/JNEUROSCI.18-19-07779.1998
Liu WS, Pesold C, Rodriguez MA, et al. Down-regulation of dendritic spine and glutamic acid decarboxylase 67 expressions in the reelin haploinsufficient heterozygous reeler mouse. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A; 2001;98(6): 3477–3482. doi:10.1073/PNAS.051614698
Bosch C, Masachs N, Exposito-Alonso D, et al. Reelin Regulates the Maturation of Dendritic Spines, Synaptogenesis and Glial Ensheathment of Newborn Granule Cells. Cerebral cortex (New York, N.Y. : 1991). Cereb Cortex; 2016;26(11): 4282–4298. doi:10.1093/CERCOR/BHW216
Khialeeva E, Carpenter EM. Nonneuronal roles for the reelin signaling pathway. Developmental dynamics : an official publication of the American Association of Anatomists. Dev Dyn; 2017;246(4): 217–226. doi:10.1002/DVDY.24462
Impagnatiello F, Guidotti AR, Pesold C, et al. A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A; 1998;95(26): 15718–15723. doi:10.1073/PNAS.95.26.15718
Zhubi A, Chen Y, Guidotti A, et al. Epigenetic regulation of RELN and GAD1 in the frontal cortex (FC) of autism spectrum disorder (ASD) subjects. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience. Int J Dev Neurosci; 2017;62: 63–72. doi:10.1016/J.IJDEVNEU.2017.02.003
Grayson DR, Jia X, Chen Y, et al. Reelin promoter hypermethylation in schizophrenia. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A; 2005;102(26): 9341–9346. doi:10.1073/PNAS.0503736102
Tueting P, Costa E, Dwivedi Y, et al. The phenotypic characteristics of heterozygous reeler mouse. Neuroreport. Neuroreport; 1999;10(6): 1329–1334. doi:10.1097/00001756-199904260-00032
Lane-Donovan C, Philips GT, Wasser CR, et al. Reelin protects against amyloid β toxicity in vivo. Science signaling. Sci Signal; 2015;8(384). doi:10.1126/SCISIGNAL.AAA6674
Dazzo E, Fanciulli M, Serioli E, et al. Heterozygous reelin mutations cause autosomal-dominant lateral temporal epilepsy. American journal of human genetics. Am J Hum Genet; 2015;96(6): 992–1000. doi:10.1016/J.AJHG.2015.04.020
Bersani G, Taddei I, Manuali G, et al. Severity of obstetric complications and risk of adult schizophrenia in male patients: a case-control study. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. J Matern Fetal Neonatal Med; 2003;14(1): 35–38. doi:10.1080/JMF.14.1.35.38
Cannon M, Jones PB, Murray RM. Obstetric complications and schizophrenia: historical and meta-analytic review. The American journal of psychiatry. Am J Psychiatry; 2002;159(7): 1080–1092. doi:10.1176/APPI.AJP.159.7.1080
Glantz LA, Lewis DA. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Archives of general psychiatry. Arch Gen Psychiatry; 2000;57(1): 65–73. doi:10.1001/ARCHPSYC.57.1.65
Bourgeois JP, Goldman-Rakic PS, Rakic P. Synaptogenesis in the prefrontal cortex of rhesus monkeys. Cerebral cortex (New York, N.Y. : 1991). Cereb Cortex; 1994;4(1): 78–96. doi:10.1093/CERCOR/4.1.78
Broadbelt K, Byne W, Jones LB. Evidence for a decrease in basilar dendrites of pyramidal cells in schizophrenic medial prefrontal cortex. Schizophrenia Research. Schizophr Res; 2002;58(1): 75–81. doi:10.1016/S0920-9964(02)00201-3
Hyman SE, Nestler EJ. Initiation and adaptation: a paradigm for understanding psychotropic drug action. The American journal of psychiatry. Am J Psychiatry; 1996;153(2): 151–162. doi:10.1176/AJP.153.2.151
McGlashan TH, Hoffman RE. Schizophrenia as a disorder of developmentally reduced synaptic connectivity. Archives of general psychiatry. Arch Gen Psychiatry; 2000;57(7): 637–648. doi:10.1001/ARCHPSYC.57.7.637
Chakos MH, Lieberman JA, Alvir J, et al. Caudate nuclei volumes in schizophrenic patients treated with typical antipsychotics or clozapine. Lancet (London, England). Lancet; 1995;345(8947): 456–457. doi:10.1016/S0140-6736(95)90441-7
Chakos MH, Lieberman JA, Bilder RM, et al. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. The American journal of psychiatry. Am J Psychiatry; 1994;151(10): 1430–1436. doi:10.1176/AJP.151.10.1430
Chakos MH, Shirakawa O, Lieberman J, et al. Striatal enlargement in rats chronically treated with neuroleptic. Biological psychiatry. Biol Psychiatry; 1998;44(8): 675–684. doi:10.1016/S0006-3223(98)00029-8
Benes FM, Paskevich PA, Domesick VB. Haloperidol-induced plasticity of axon terminals in rat substantia nigra. Science (New York, N.Y.). Science; 1983;221(4614): 969–971. doi:10.1126/SCIENCE.6879197
Benes FM, Paskevich PA, Davidson J, et al. Synaptic rearrangements in medial prefrontal cortex of haloperidol-treated rats. Brain research. Brain Res; 1985;348(1): 15–20. doi:10.1016/0006-8993(85)90353-1
Greengard P, Valtorta F, Czernik AJ, et al. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science (New York, N.Y.). Science; 1993;259(5096): 780–785. doi:10.1126/SCIENCE.8430330
Schulman H. Protein phosphorylation in neuronal plasticity and gene expression. Current opinion in neurobiology. Curr Opin Neurobiol; 1995;5(3): 375–381. doi:10.1016/0959-4388(95)80051-4
Frank DA, Greenberg ME. CREB: a mediator of long-term memory from mollusks to mammals. Cell. Cell; 1994;79(1): 5–8. doi:10.1016/0092-8674(94)90394-8
Deutch AY, Duman RS. The effects of antipsychotic drugs on Fos protein expression in the prefrontal cortex: cellular localization and pharmacological characterization. Neuroscience. Neuroscience; 1996;70(2): 377–389. doi:10.1016/0306-4522(95)00357-6
MacGibbon GA, Lawlor PA, Bravo R, et al. Clozapine and haloperidol produce a differential pattern of immediate early gene expression in rat caudate-putamen, nucleus accumbens, lateral septum and islands of Calleja. Brain research. Molecular brain research. Brain Res Mol Brain Res; 1994;23(1–2): 21–32. doi:10.1016/0169-328X(94)90207-0
Kelley AE. Memory and addiction: Shared neural circuitry and molecular mechanisms. Neuron. Neuron; 2004;44(1): 161–179. doi:10.1016/j.neuron.2004.09.016
Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: the role of reward-related learning and memory. Annual review of neuroscience. Annu Rev Neurosci; 2006;29: 565–598. doi:10.1146/ANNUREV.NEURO.29.051605.113009
Volkow ND, Baler RD, Compton WM, et al. Adverse health effects of marijuana use. The New England journal of medicine. N Engl J Med; 2014;370(23): 2219–2227. doi:10.1056/NEJMRA1402309
Goodman J, Packard MG. Memory Systems and the Addicted Brain. Frontiers in psychiatry. Front Psychiatry; 2016;7(FEB). doi:10.3389/FPSYT.2016.00024
Smith DM, Mizumori SJY. Hippocampal place cells, context, and episodic memory. Hippocampus. Hippocampus; 2006;16(9): 716–729. doi:10.1002/HIPO.20208
Ornstein TJ, Iddon JL, Baldacchino AM, et al. Profiles of cognitive dysfunction in chronic amphetamine and heroin abusers. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Neuropsychopharmacology; 2000;23(2): 113–126. doi:10.1016/S0893-133X(00)00097-X
Robbins TW, Ersche KD, Everitt BJ. Drug addiction and the memory systems of the brain. Annals of the New York Academy of Sciences. Ann N Y Acad Sci; 2008;1141: 1–21. doi:10.1196/ANNALS.1441.020
Stavro K, Pelletier J, Potvin S. Widespread and sustained cognitive deficits in alcoholism: a meta-analysis. Addiction biology. Addict Biol; 2013;18(2): 203–213. doi:10.1111/J.1369-1600.2011.00418.X
Solowij N. Do cognitive impairments recover following cessation of cannabis use? Life sciences. Life Sci; 1995;56(23–24): 2119–2126. doi:10.1016/0024-3205(95)00197-E
Jacobsen LK, Krystal JH, Mencl WE, et al. Effects of smoking and smoking abstinence on cognition in adolescent tobacco smokers. Biological psychiatry. Biol Psychiatry; 2005;57(1): 56–66. doi:10.1016/J.BIOPSYCH.2004.10.022
Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. The American journal of psychiatry. Am J Psychiatry; 1985;142(11): 1259–1264. doi:10.1176/AJP.142.11.1259
Rukstalis M, Jepson C, Patterson F, et al. Increases in hyperactive-impulsive symptoms predict relapse among smokers in nicotine replacement therapy. Journal of substance abuse treatment. J Subst Abuse Treat; 2005;28(4): 297–304. doi:10.1016/J.JSAT.2005.02.002
Patterson F, Jepson C, Loughead J, et al. Working memory deficits predict short-term smoking resumption following brief abstinence. Drug and alcohol dependence. Drug Alcohol Depend; 2010;106(1): 61–64. doi:10.1016/J.DRUGALCDEP.2009.07.020
Wood SC, Fay J, Sage JR, et al. Cocaine and Pavlovian fear conditioning: dose-effect analysis. Behavioural brain research. Behav Brain Res; 2007;176(2): 244–250. doi:10.1016/J.BBR.2006.10.008
Colrain IM, Mangan GL, Pellett OL, et al. Effects of post-learning smoking on memory consolidation. Psychopharmacology. Psychopharmacology (Berl); 1992;108(4): 448–451. doi:10.1007/BF02247419
Ito R, Canseliet M. Amphetamine exposure selectively enhances hippocampus-dependent spatial learning and attenuates amygdala-dependent cue learning. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. Neuropsychopharmacology; 2010;35(7): 1440–1452. doi:10.1038/NPP.2010.14
Berry RB, Matthews DB. Acute ethanol administration selectively impairs spatial memory in C57BL/ 6J mice. Alcohol. Alcohol; 2004;32(1): 9–18. doi:10.1016/j.alcohol.2003.09.005
Eisch AJ, Barrot M, Schad CA, et al. Opiates inhibit neurogenesis in the adult rat hippocampus. Proceedings of the National Academy of Sciences of the United States of America. Proc Natl Acad Sci U S A; 2000;97(13): 7579–7584. doi:10.1073/PNAS.120552597
Morón JA, Abul-Husn NS, Rozenfeld R, et al. Morphine administration alters the profile of hippocampal postsynaptic density-associated proteins: a proteomics study focusing on endocytic proteins. Molecular & cellular proteomics : MCP. Mol Cell Proteomics; 2007;6(1): 29–42. doi:10.1074/MCP.M600184-MCP200
Ranganathan M, D’Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology. Psychopharmacology (Berl); 2006;188(4): 425–444. doi:10.1007/S00213-006-0508-Y
Gu H, Salmeron BJ, Ross TJ, et al. Mesocorticolimbic circuits are impaired in chronic cocaine users as demonstrated by resting-state functional connectivity. NeuroImage. Neuroimage; 2010;53(2): 593–601. doi:10.1016/J.NEUROIMAGE.2010.06.066
Johanson CE, Frey KA, Lundahl LH, et al. Cognitive function and nigrostriatal markers in abstinent methamphetamine abusers. Psychopharmacology. Psychopharmacology (Berl); 2006;185(3): 327–338. doi:10.1007/S00213-006-0330-6
Yamazaki Y, Fujii S, Jia Y, et al. Nicotine withdrawal suppresses nicotinic modulation of long-term potentiation induction in the hippocampal CA1 region. The European journal of neuroscience. Eur J Neurosci; 2006;24(10): 2903–2916. doi:10.1111/J.1460-9568.2006.05160.X
Hoffman AF, Oz M, Yang R, et al. Opposing actions of chronic Delta9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation. Learning & memory (Cold Spring Harbor, N.Y.). Learn Mem; 2007;14(1–2): 63–74. doi:10.1101/LM.439007
Li Z, Wu CF, Pei G, et al. Reversal of morphine-induced memory impairment in mice by withdrawal in Morris water maze: possible involvement of cholinergic system. Pharmacology, biochemistry, and behavior. Pharmacol Biochem Behav; 2001;68(3): 507–513. doi:10.1016/S0091-3057(01)00456-7
Ma MX, Chen YM, He J, et al. Effects of morphine and its withdrawal on Y-maze spatial recognition memory in mice. Neuroscience. Neuroscience; 2007;147(4): 1059–1065. doi:10.1016/J.NEUROSCIENCE.2007.05.020
