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Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection

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Abstract

During the past two decades, there has been a tremendous expansion of knowledge regarding the neurobiological effects of substance abuse and how these effects impact behavior. At the same time, there has been a profound change in our understanding of the way in which the central nervous system responds to noxious stimuli. Most often referred to as the innate immune response (IIR), this defense mechanism is activated by a number of agents (toxic, microbial, ischemic) and has been implicated in the progression of a number of neurodegenerative diseases. We review evidence that psychostimulants of abuse (cocaine, methamphetamine, ecstasy) are associated with activation of the IIR. We first present background on what is currently known about the IIR including some of the cellular elements involved (microglia, astrocytes, vascular endothelial cells), key receptor pathways, and primary inflammatory cytokines (IL-1β, IL-6, TNF-α). We then present a variety of protein and gene expression data taken from animal studies that show increased expression of various components of the IIR following acute or repeated psychostimulant administration. Collectively the data indicate an association of psychostimulant use with IIR activation in the brain even at exposures not traditionally associated with neurotoxicity. Thus, the gradually escalating deleterious effects of psychostimulant use could in part involve neuroinflammatory mechanisms. Finally, we offer one hypothesis of a possible mechanism by which psychostimulants result in IIR activation and discuss the potential therapeutic implications of these findings for treatment of the recovering addict.

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Abbreviations

(i)NOS:

(Inducible) nitric oxide synthase

ADAM:

A disintegrin and metalloproteinase

ADAMts:

A disintegrin and metalloproteinase and thrombospondin

AP-2:

Activator protein-2

Areg:

Amphiregulin

BBB:

Blood–brain barrier

Bcl-2:

B cell lymphoma 2

BDNF:

Brain-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

BMP:

Bone morphogenetic protein

CDH:

Cadherin

cFOS:

FBJ murine osteosarcoma viral oncogene homolog

CLDN:

Claudin

CXCL:

Chemokine ligand

CXCR:

Chemokine receptor

DAMP:

Damage-associated molecular pattern

EDN:

Endothelin

EGF:

Epidermal growth factor

EGR:

Early growth response protein

GDNF:

Glial-derived neurotrophic factor

IFN:

Interferon

IGF:

Insulin-like growth factor

IIR:

Innate immune response

IL:

Interleukin

iVGF:

Inducible nerve growth factor

JAM:

Junction adhesion molecule

LIF:

Leukemia inhibitory factor

MCP-1:

Monocyte chemotactic protein-1

MCSF:

Macrophage colony stimulating factor

MHC-II:

Major histocompatibility complex II

MMP:

Matrix metalloproteinase

NF-κB:

Nuclear factor-kappaB

NGF:

Nerve growth factor

NOSTRIN:

Nitric oxide synthase trafficker protein

NT:

Neurotrophin

OCLN:

Occludin

PAMP:

Pathogen-associated molecular pattern

PDGF:

Platelet-derived growth factor

Poly(I:C):

Polyinosinic:polycytidylic acid

SOD:

Superoxide dismutase

TGF-β:

Transforming growth factor-beta

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

VEGF:

Vascular endothelial growth factor

References

  • Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev 7(1):41–53

    Article  CAS  Google Scholar 

  • Ahmed SH, Lutjens R, van der Stap LD, Lekic D, Romano-Spica V, Morales M, Koob GF, Repunte-Canonigo V, Sanna PP (2005) Gene expression evidence for remodeling of lateral hypothalamic circuitry in cocaine addiction. Proc Natl Acad Sci USA 102(32):11533–11538

    Article  PubMed  CAS  Google Scholar 

  • Alia-Klein N, Parvaz MA, Woicik PA, Konova AB, Maloney T, Shumay E, Wang R, Telang F, Biegon A, Wang GJ, Fowler JS, Tomasi D, Volkow ND, Goldstein RZ (2011) Gene × disease interaction on orbitofrontal gray matter in cocaine addiction. Arch Gen Psychiatry 68(3):283–294

    Article  PubMed  Google Scholar 

  • Asanuma M, Miyazaki I, Higashi Y, Tsuji T, Ogawa N (2004) Specific gene expression and possible involvement of inflammation in methamphetamine-induced neurotoxicity. Ann NY Acad Sci 1025:69–75

    Article  PubMed  CAS  Google Scholar 

  • Baeg EH, Jackson ME, Jedema HP, Bradberry CW (2009) Orbitofrontal and anterior cingulate cortex neurons selectively process cocaine-associated environmental cues in the rhesus monkey. J Neurosci 29(37):11619–11627

    Article  PubMed  CAS  Google Scholar 

  • Barrett AE, Turner RJ (2006) Family structure and substance use problems in adolescence and early adulthood: examining explanations for the relationship. Addiction 101(1):109–120

    Article  PubMed  Google Scholar 

  • Bartzokis G, Beckson M, Lu PH, Edwards N, Bridge P, Mintz J (2002) Brain maturation may be arrested in chronic cocaine addicts. Biol Psychiatry 51(8):605–611

    Article  PubMed  CAS  Google Scholar 

  • Basu A, Krady JK, O’Malley M, Styren SD, DeKosky ST, Levison SW (2002) The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. J Neurosci 22(14):6071–6082

    PubMed  CAS  Google Scholar 

  • Block ML, Zecca L, Hong JS (2007) Microglia-mediated neurotoxicity: uncovering the molecular mechanisms. Nat Rev 8(1):57–69

    Article  CAS  Google Scholar 

  • Bowyer JF, Pogge AR, Delongchamp RR, O’Callaghan JP, Patel KM, Vrana KE, Freeman WM (2007) A threshold neurotoxic amphetamine exposure inhibits parietal cortex expression of synaptic plasticity-related genes. Neuroscience 144(1):66–76

    Article  PubMed  CAS  Google Scholar 

  • Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR (2005) Inhibition of astroglial nuclear factor kappaB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 202(1):145–156

    Article  PubMed  CAS  Google Scholar 

  • Breslau N, Davis GC, Schultz LR (2003) Posttraumatic stress disorder and the incidence of nicotine, alcohol, and other drug disorders in persons who have experienced trauma. Arch Gen Psychiatry 60(3):289–294

    Article  PubMed  Google Scholar 

  • Brown TE, Forquer MR, Harding JW, Wright JW, Sorg BA (2008) Increase in matrix metalloproteinase-9 levels in the rat medial prefrontal cortex after cocaine reinstatement of conditioned place preference. Synapse 62(12):886–889

    Article  PubMed  CAS  Google Scholar 

  • Cadet JL, Jayanthi S, McCoy MT, Vawter M, Ladenheim B (2001) Temporal profiling of methamphetamine-induced changes in gene expression in the mouse brain: evidence from cDNA array. Synapse 41(1):40–48

    Article  PubMed  CAS  Google Scholar 

  • Cadet JL, Krasnova IN, Jayanthi S, Lyles J (2007) Neurotoxicity of substituted amphetamines: molecular and cellular mechanisms. Neurotox Res 11(3–4):183–202

    Article  PubMed  CAS  Google Scholar 

  • Carpentier PA, Begolka WS, Olson JK, Elhofy A, Karpus WJ, Miller SD (2005) Differential activation of astrocytes by innate and adaptive immune stimuli. Glia 49(3):360–374

    Article  PubMed  Google Scholar 

  • Chen J, Buchanan JB, Sparkman NL, Godbout JP, Freund GG, Johnson RW (2008) Neuroinflammation and disruption in working memory in aged mice after acute stimulation of the peripheral innate immune system. Brain Behav Immun 22(3):301–311

    Article  PubMed  CAS  Google Scholar 

  • Crews FT, Zou J, Qin L (2011) Induction of innate immune genes in brain create the neurobiology of addiction. Brain Behav Immun 25(Suppl 1):S4–S12

    Article  PubMed  CAS  Google Scholar 

  • Dantzer R (2001) Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 15(1):7–24

    Article  PubMed  CAS  Google Scholar 

  • Dantzer R, Kelley KW (1989) Stress and immunity: an integrated view of relationships between the brain and the immune system. Life Sci 44(26):1995–2008

    Article  PubMed  CAS  Google Scholar 

  • Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW (2008) From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev 9(1):46–56

    Article  CAS  Google Scholar 

  • Decker EL, Nehmann N, Kampen E, Eibel H, Zipfel PF, Skerka C (2003) Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression. Nucleic Acids Res 31(3):911–921

    Article  PubMed  CAS  Google Scholar 

  • Dehouck MP, Meresse S, Delorme P, Fruchart JC, Cecchelli R (1990) An easier, reproducible, and mass-production method to study the blood-brain barrier in vitro. J Neurochem 54(5):1798–1801

    Article  PubMed  CAS  Google Scholar 

  • Farina C, Aloisi F, Meinl E (2007) Astrocytes are active players in cerebral innate immunity. Trends Immunol 28(3):138–145

    Article  PubMed  CAS  Google Scholar 

  • Frank MG, Baratta MV, Sprunger DB, Watkins LR, Maier SF (2007) Microglia serve as a neuroimmune substrate for stress-induced potentiation of CNS pro-inflammatory cytokine responses. Brain Behav Immun 21(1):47–59

    Article  PubMed  CAS  Google Scholar 

  • Franklin TR, Acton PD, Maldjian JA, Gray JD, Croft JR, Dackis CA, O’Brien CP, Childress AR (2002) Decreased gray matter concentration in the insular, orbitofrontal, cingulate, and temporal cortices of cocaine patients. Biol Psychiatry 51(2):134–142

    Article  PubMed  CAS  Google Scholar 

  • Fuhrman M, Bittner T, Jung CK, Burgold S, Page RM, Mitteregger G, Haass C, Laferla FM, Kretzschmar H, Herms J (2010) Microglial Cx3cr1 knockout prevents neuron loss in a mouse model of Alzheimer’s disease. Nat Neurosci 13(4):411–413

    Article  CAS  Google Scholar 

  • Garavan H, Pankiewicz J, Bloom A, Cho JK, Sperry L, Ross TJ, Salmeron BJ, Risinger R, Kelley D, Stein EA (2000) Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry 157(11):1789–1798

    Article  PubMed  CAS  Google Scholar 

  • Godbout JP, Johnson RW (2009) Age and neuroinflammation: a lifetime of psychoneuroimmune consequences. Immunol Allergy Clin North Am 29(2):321–337

    Article  PubMed  Google Scholar 

  • Godbout JP, Chen J, Abraham J, Richwine AF, Berg BM, Kelley KW, Johnson RW (2005) Exaggerated neuroinflammation and sickness behavior in aged mice following activation of the peripheral innate immune system. FASEB J 19(10):1329–1331

    PubMed  CAS  Google Scholar 

  • Goldstein RZ, Alia-Klein N, Tomasi D, Zhang L, Cottone LA, Maloney T, Telang F, Caparelli EC, Chang L, Ernst T, Samaras D, Squires NK, Volkow ND (2007) Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? Am J Psychiatry 164(1):43–51

    Article  PubMed  Google Scholar 

  • Goldstein RZ, Alia-Klein N, Tomasi D, Carrillo JH, Maloney T, Woicik PA, Wang R, Telang F, Volkow ND (2009) Anterior cingulate cortex hypoactivations to an emotionally salient task in cocaine addiction. Proc Natl Acad Sci USA 106(23):9453–9458

    Article  PubMed  CAS  Google Scholar 

  • Goncalves J, Martins T, Ferreira R, Milhazes N, Borges F, Ribeiro CF, Malva JO, Macedo TR, Silva AP (2008) Methamphetamine-induced early increase of IL-6 and TNF-alpha mRNA expression in the mouse brain. Ann NY Acad Sci 1139:103–111

    Article  PubMed  CAS  Google Scholar 

  • Goncalves J, Baptista S, Martins T, Milhazes N, Borges F, Ribeiro CF, Malva JO, Silva AP (2010) Methamphetamine-induced neuroinflammation and neuronal dysfunction in the mice hippocampus: preventive effect of indomethacin. Eur J Neurosci 31(2):315–326

    Article  PubMed  Google Scholar 

  • Gordon S (2007) The macrophage: past, present and future. Eur J Immunol 37(Suppl 1):S9–S17

    Article  PubMed  CAS  Google Scholar 

  • Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS, Margolin A (1996) Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci USA 93(21):12040–12045

    Article  PubMed  CAS  Google Scholar 

  • Griffin WS, Sheng JG, Gentleman SM, Graham DI, Mrak RE, Roberts GW (1994) Microglial interleukin-1 alpha expression in human head injury: correlations with neuronal and neuritic beta-amyloid precursor protein expression. Neurosci Lett 176(2):133–136

    Article  PubMed  CAS  Google Scholar 

  • Griffin WS, Sheng JG, Roberts GW, Mrak RE (1995) Interleukin-1 expression in different plaque types in Alzheimer’s disease: significance in plaque evolution. J Neuropathol Exp Neurol 54(2):276–281

    Article  PubMed  CAS  Google Scholar 

  • Hanisch UK, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10(11):1387–1394

    Article  PubMed  CAS  Google Scholar 

  • Hart BL (1988) Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 12(2):123–137

    Article  PubMed  CAS  Google Scholar 

  • Heppner FL, Greter M, Marino D, Falsig J, Raivich G, Hovelmeyer N, Waisman A, Rulicke T, Prinz M, Priller J, Becher B, Aguzzi A (2005) Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nat Med 11(2):146–152

    Article  PubMed  CAS  Google Scholar 

  • Honkaniemi J, Sharp FR (1996) Global ischemia induces immediate-early genes encoding zinc finger transcription factors. J Cereb Blood Flow Metab 16(4):557–565

    Article  PubMed  CAS  Google Scholar 

  • Hyman SE, Malenka RC, Nestler EJ (2006) Neural Mechanisms of Addiction: The Role of Reward-Related Learning and Memory. Annu Rev Neurosci 29:565–598

    Article  PubMed  CAS  Google Scholar 

  • Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, Kamimura Y, Furuuchi K, Kokai Y, Nakagawa T, Mori M, Sawada N (1999) Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier. Biochem Biophys Res Commun 261(1):108–112

    Article  PubMed  CAS  Google Scholar 

  • Jack CS, Arbour N, Manusow J, Montgrain V, Blain M, McCrea E, Shapiro A, Antel JP (2005) TLR signaling tailors innate immune responses in human microglia and astrocytes. J Immunol 175(7):4320–4330

    PubMed  CAS  Google Scholar 

  • Jedema HP, Moghaddam B (1994) Glutamatergic control of dopamine release during stress in the rat prefrontal cortex. J Neurochem 63(2):785–788

    Article  PubMed  CAS  Google Scholar 

  • Jentsch JD, Taylor JR (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 146(4):373–390

    Article  PubMed  CAS  Google Scholar 

  • Johnson JD, O’Connor KA, Deak T, Spencer RL, Watkins LR, Maier SF (2002) Prior stressor exposure primes the HPA axis. Psychoneuroendocrinology 27(3):353–365

    Article  PubMed  CAS  Google Scholar 

  • Kalivas PW, Volkow ND (2005) The neural basis of addiction: a pathology of motivation and choice. Am J Psychiatry 162(8):1403–1413

    Article  PubMed  Google Scholar 

  • Kawahara N, Wang Y, Mukasa A, Furuya K, Shimizu T, Hamakubo T, Aburatani H, Kodama T, Kirino T (2004) Genome-wide gene expression analysis for induced ischemic tolerance and delayed neuronal death following transient global ischemia in rats. J Cereb Blood Flow Metab 24(2):212–223

    Article  PubMed  CAS  Google Scholar 

  • Kofler J, Wiley CA (2011) Microglia: key innate immune cells of the brain. Toxicol Pathol 39(1):103–114

    Article  PubMed  Google Scholar 

  • Koob GF, Bloom FE (1988) Cellular and molecular mechanisms of drug dependence. Science 242(4879):715–723

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis [Review]. Neuropsychopharmacology 24(2):97–129

    Article  PubMed  CAS  Google Scholar 

  • Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19(8):312–318

    Article  PubMed  CAS  Google Scholar 

  • LaVoie MJ, Card JP, Hastings TG (2004) Microglial activation precedes dopamine terminal pathology in methamphetamine-induced neurotoxicity. Exp Neurol 187(1):47–57

    Article  PubMed  CAS  Google Scholar 

  • Lee CT, Lehrmann E, Hayashi T, Amable R, Tsai SY, Chen J, Sanchez JF, Shen J, Becker KG, Freed WJ (2009) Gene expression profiling reveals distinct cocaine-responsive genes in human fetal CNS cell types. J Addict Med 3(4):218–226

    Article  PubMed  CAS  Google Scholar 

  • Lehnardt S (2010) Innate immunity and neuroinflammation in the CNS: the role of microglia in Toll-like receptor-mediated neuronal injury. Glia 58(3):253–263

    PubMed  Google Scholar 

  • Liberto CM, Albrecht PJ, Herx LM, Yong VW, Levison SW (2004) Pro-regenerative properties of cytokine-activated astrocytes. J Neurochem 89(5):1092–1100

    Article  PubMed  CAS  Google Scholar 

  • Lim KO, Wozniak JR, Mueller BA, Franc DT, Specker SM, Rodriguez CP, Silverman AB, Rotrosen JP (2008) Brain macrostructural and microstructural abnormalities in cocaine dependence. Drug Alcohol Depend 92(1–3):164–172

    Article  PubMed  CAS  Google Scholar 

  • Lin KY, Cherng CG, Yang FR, Lin LC, Lu RB, Yu L (2011) Memantine abolishes the formation of cocaine-induced conditioned place preference possibly via its IL-6-modulating effect in medial prefrontal cortex. Behav Brain Res 220(1):126–131

    Article  PubMed  CAS  Google Scholar 

  • Little KY, Ramssen E, Welchko R, Volberg V, Roland CJ, Cassin B (2009) Decreased brain dopamine cell numbers in human cocaine users. Psychiatry Res 168(3):173–180

    Article  PubMed  CAS  Google Scholar 

  • Liu B, Chen H, Johns TG, Neufeld AH (2006) Epidermal growth factor receptor activation: an upstream signal for transition of quiescent astrocytes into reactive astrocytes after neural injury. J Neurosci 26(28):7532–7540

    Article  PubMed  CAS  Google Scholar 

  • Loftis JM, Choi D, Hoffman W, Huckans MS (2011) Methamphetamine causes persistent immune dysregulation: a cross-species, translational report. Neurotox Res 20(1):59–68

    Article  PubMed  CAS  Google Scholar 

  • Lu DY, Liou HC, Tang CH, Fu WM (2006) Hypoxia-induced iNOS expression in microglia is regulated by the PI3-kinase/Akt/mTOR signaling pathway and activation of hypoxia inducible factor-1alpha. Biochem Pharmacol 72(8):992–1000

    Article  PubMed  CAS  Google Scholar 

  • Lynch MA (2009) The multifaceted profile of activated microglia. Mol Neurobiol 40(2):139–156

    Article  PubMed  CAS  Google Scholar 

  • Mark KS, Davis TP (2002) Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation. Am J Physiol Heart Circ Physiol 282(4):H1485–H1494

    PubMed  CAS  Google Scholar 

  • McFarland K, Lapish CC, Kalivas PW (2003) Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 23(8):3531–3537

    PubMed  CAS  Google Scholar 

  • McGeer PL, McGeer EG (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 21(2):195–218

    Article  PubMed  CAS  Google Scholar 

  • McGeer PL, Yasojima K, McGeer EG (2002) Association of interleukin-1 beta polymorphisms with idiopathic Parkinson’s disease. Neurosci Lett 326(1):67–69

    Article  PubMed  CAS  Google Scholar 

  • McKay JR, Alterman AI, Mulvaney FD, Koppenhaver JM (1999) Predicting proximal factors in cocaine relapse and near miss episodes: clinical and theoretical implications. Drug Alcohol Depend 56(1):67–78

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin J, See RE (2003) Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats. Psychopharmacology 168(1–2):57–65

    Article  PubMed  CAS  Google Scholar 

  • Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C (2002) The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 202(1–2):13–23

    Article  PubMed  CAS  Google Scholar 

  • Mizoguchi H, Yamada K, Niwa M, Mouri A, Mizuno T, Noda Y, Nitta A, Itohara S, Banno Y, Nabeshima T (2007) Reduction of methamphetamine-induced sensitization and reward in matrix metalloproteinase-2 and -9-deficient mice. J Neurochem 100(6):1579–1588

    PubMed  CAS  Google Scholar 

  • Mizoguchi H, Yamada K, Nabeshima T (2008) Neuropsychotoxicity of abused drugs: involvement of matrix metalloproteinase-2 and -9 and tissue inhibitor of matrix metalloproteinase-2 in methamphetamine-induced behavioral sensitization and reward in rodents. J Pharmacol Sci 106(1):9–14

    Article  PubMed  CAS  Google Scholar 

  • Moghaddam B (1993) Stress preferentially increases extraneuronal levels of excitatory amino acids in the prefrontal cortex: comparison to hippocampus and basal ganglia. J Neurochem 60(5):1650–1657

    Article  PubMed  CAS  Google Scholar 

  • Moghaddam B, Bolinao ML, Steinbehrens B, Sapolsky R (1994) Glucocorticoids mediate the stress-induced extracellular accumulation of glutamate. Brain Res 655(1–2):251–254

    Article  PubMed  CAS  Google Scholar 

  • Mojsilovic-Petrovic J, Callaghan D, Cui H, Dean C, Stanimirovic DB, Zhang W (2007) Hypoxia-inducible factor-1 (HIF-1) is involved in the regulation of hypoxia-stimulated expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and MCP-5 (Ccl12) in astrocytes. J Neuroinflammation 4:12

    Article  PubMed  Google Scholar 

  • Myer DJ, Gurkoff GG, Lee SM, Hovda DA, Sofroniew MV (2006) Essential protective roles of reactive astrocytes in traumatic brain injury. Brain: a journal of neurology 129(Pt 10):2761–2772

    Article  CAS  Google Scholar 

  • Nair A, Bonneau RH (2006) Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation. J Neuroimmunol 171(1–2):72–85

    Article  PubMed  CAS  Google Scholar 

  • Neisewander JL, Baker DA, Fuchs RA, Tran-Nguyen LT, Palmer A, Marshall JF (2000) Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment. J Neurosci 20(2):798–805

    PubMed  CAS  Google Scholar 

  • Newcomb MD, Harlow LL (1986) Life events and substance use among adolescents: mediating effects of perceived loss of control and meaninglessness in life. J Pers Soc Psychol 51(3):564–577

    Article  PubMed  CAS  Google Scholar 

  • Newcombe J, Uddin A, Dove R, Patel B, Turski L, Nishizawa Y, Smith T (2008) Glutamate receptor expression in multiple sclerosis lesions. Brain Pathol 18(1):52–61

    Article  PubMed  Google Scholar 

  • Noda M, Nakanishi H, Nabekura J, Akaike N (2000) AMPA-kainate subtypes of glutamate receptor in rat cerebral microglia. J Neurosci 20(1):251–258

    PubMed  CAS  Google Scholar 

  • O’Neill J, Cardenas VA, Meyerhoff DJ (2001) Effects of abstinence on the brain: quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse. Alcohol Clin Exp Res 25(11):1673–1682

    Article  PubMed  Google Scholar 

  • Petty MA, Lo EH (2002) Junctional complexes of the blood-brain barrier: permeability changes in neuroinflammation. Prog Neurobiol 68(5):311–323

    Article  PubMed  CAS  Google Scholar 

  • Piechota M, Korostynski M, Solecki W, Gieryk A, Slezak M, Bilecki W, Ziolkowska B, Kostrzewa E, Cymerman I, Swiech L, Jaworski J, Przewlocki R (2010) The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum. Genome Biol 11(5):R48

    Article  PubMed  CAS  Google Scholar 

  • Porrino LJ, Lyons D (2000) Orbital and medial prefrontal cortex and psychostimulant abuse: studies in animal models. Cereb Cortex 10(3):326–333

    Article  PubMed  CAS  Google Scholar 

  • Porter JN, Olsen AS, Gurnsey K, Dugan BP, Jedema HP, Bradberry CW (2011) Chronic cocaine self-administration in rhesus monkeys: impact on associative learning, cognitive control, and working memory. J Neurosci 31(13):4926–4934

    Article  PubMed  CAS  Google Scholar 

  • Renthal W, Maze I, Krishnan V, Covington HE 3rd, Xiao G, Kumar A, Russo SJ, Graham A, Tsankova N, Kippin TE, Kerstetter KA, Neve RL, Haggarty SJ, McKinsey TA, Bassel-Duby R, Olson EN, Nestler EJ (2007) Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 56(3):517–529

    Article  PubMed  CAS  Google Scholar 

  • Roberts DCS, Koob GF, Klonoff P, Fibiger HC (1980) Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol Biochem Behav 12(5):781–787

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2008) Review. The incentive sensitization theory of addiction: some current issues. Philos Trans R Soc Lond 363(1507):3137–3146

    Article  Google Scholar 

  • Rosenberg GA (2002) Matrix metalloproteinases in neuroinflammation. Glia 39(3):279–291

    Article  PubMed  Google Scholar 

  • Rosenberg GA (2009) Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol 8(2):205–216

    Article  PubMed  CAS  Google Scholar 

  • Rubin LL, Hall DE, Porter S, Barbu K, Cannon C, Horner HC, Janatpour M, Liaw CW, Manning K, Morales J et al (1991) A cell culture model of the blood-brain barrier. J Cell Biol 115(6):1725–1735

    Article  PubMed  CAS  Google Scholar 

  • 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 (2008) Methamphetamine causes microglial activation in the brains of human abusers. J Neurosci 28(22):5756–5761

    Article  PubMed  CAS  Google Scholar 

  • Sher KJ, Walitzer KS, Wood PK, Brent EE (1991) Characteristics of children of alcoholics: putative risk factors, substance use and abuse, and psychopathology. J Abnorm Psychol 100(4):427–448

    Article  PubMed  CAS  Google Scholar 

  • Shoyab M, Plowman GD, McDonald VL, Bradley JG, Todaro GJ (1989) Structure and function of human amphiregulin: a member of the epidermal growth factor family. Science 243(4894 Pt 1):1074–1076

    Article  PubMed  CAS  Google Scholar 

  • Sim ME, Lyoo IK, Streeter CC, Covell J, Sarid-Segal O, Ciraulo DA, Kim MJ, Kaufman MJ, Yurgelun-Todd DA, Renshaw PF (2007) Cerebellar gray matter volume correlates with duration of cocaine use in cocaine-dependent subjects. Neuropsychopharmacology 32(10):2229–2237

    Article  PubMed  CAS  Google Scholar 

  • Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology 158(4):343–359

    Article  PubMed  CAS  Google Scholar 

  • Sinha R (2007) The role of stress in addiction relapse. Curr Psychiatry Rep 9(5):388–395

    Article  PubMed  Google Scholar 

  • Streit WJ (2002) Microglia as neuroprotective, immunocompetent cells of the CNS. Glia 40(2):133–139

    Article  PubMed  Google Scholar 

  • Streit WJ (2010) Microglial activation and neuroinflammation in Alzheimer’s disease: a critical examination of recent history. Front Aging Neurosci 2:22

    PubMed  Google Scholar 

  • Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57(6):563–581

    Article  PubMed  CAS  Google Scholar 

  • Streit WJ, Sammons NW, Kuhns AJ, Sparks DL (2004) Dystrophic microglia in the aging human brain. Glia 45(2):208–212

    Article  PubMed  Google Scholar 

  • Streit WJ, Conde JR, Fendrick SE, Flanary BE, Mariani CL (2005) Role of microglia in the central nervous system’s immune response. Neurol Res 27(7):685–691

    PubMed  Google Scholar 

  • Sun W, Rebec GV (2006) Repeated cocaine self-administration alters processing of cocaine-related information in rat prefrontal cortex. J Neurosci 26(30):8004–8008

    Article  PubMed  CAS  Google Scholar 

  • Takeuchi O, Akira S (2010) Pattern recognition receptors and inflammation. Cell 140(6):805–820

    Article  PubMed  CAS  Google Scholar 

  • Ten VS, Pinsky DJ (2002) Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction. Curr Opin Crit Care 8(3):242–250

    Article  PubMed  Google Scholar 

  • Thomas DM, Kuhn DM (2005) MK-801 and dextromethorphan block microglial activation and protect against methamphetamine-induced neurotoxicity. Brain Res 1050(1–2):190–198

    Article  PubMed  CAS  Google Scholar 

  • Thomas DM, Walker PD, Benjamins JA, Geddes TJ, Kuhn DM (2004) Methamphetamine neurotoxicity in dopamine nerve endings of the striatum is associated with microglial activation. J Pharmacol Exp Ther 311(1):1–7

    Article  PubMed  CAS  Google Scholar 

  • Tilleux S, Hermans E (2007) Neuroinflammation and regulation of glial glutamate uptake in neurological disorders. J Neurosci Res 85(10):2059–2070

    Article  PubMed  CAS  Google Scholar 

  • Tomlinson KL, Tate SR, Anderson KG, McCarthy DM, Brown SA (2006) An examination of self-medication and rebound effects: psychiatric symptomatology before and after alcohol or drug relapse. Addict Behav 31(3):461–474

    Article  PubMed  Google Scholar 

  • Touzani O, Boutin H, Chuquet J, Rothwell N (1999) Potential mechanisms of interleukin-1 involvement in cerebral ischaemia. J Neuroimmunol 100(1–2):203–215

    Article  PubMed  CAS  Google Scholar 

  • Vadhan NP, Carpenter KM, Copersino ML, Hart CL, Foltin RW, Nunes EV (2007) Attentional bias towards cocaine-related stimuli: relationship to treatment-seeking for cocaine dependence. Am J Drug Alcohol Abuse 33(5):727–736

    Article  PubMed  Google Scholar 

  • Volkow ND, Fowler JS (2000) Addiction, a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cereb Cortex 10(3):318–325

    Article  PubMed  CAS  Google Scholar 

  • Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S, Sofroniew MV (2009) Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 29(37):11511–11522

    Article  PubMed  CAS  Google Scholar 

  • Williams JM, Steketee JD (2004) Cocaine increases medial prefrontal cortical glutamate overflow in cocaine-sensitized rats: a time course study. Eur J Neurosci 20(6):1639–1646

    Article  PubMed  Google Scholar 

  • Wise RA, Rompre PP (1989) Brain dopamine and reward. Annu Rev Psychol 40:191–225

    Article  PubMed  CAS  Google Scholar 

  • Wisor JP, Schmidt MA, Clegern WC (2011) Cerebral microglia mediate sleep/wake and neuroinflammatory effects of methamphetamine. Brain Behav Immun 25(4):767–776

    Article  PubMed  CAS  Google Scholar 

  • Witt KA, Mark KS, Huber J, Davis TP (2005) Hypoxia-inducible factor and nuclear factor kappa-B activation in blood–brain barrier endothelium under hypoxic/reoxygenation stress. J Neurochem 92(1):203–214

    Article  PubMed  CAS  Google Scholar 

  • Woolverton WL, Johnson KM (1992) Neurobiology of cocaine abuse. Trends Pharmacol Sci 13(5):193–200

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto BK, Moszczynska A, Gudelsky GA (2010) Amphetamine toxicities: classical and emerging mechanisms. Ann NY Acad Sci 1187:101–121

    Article  PubMed  CAS  Google Scholar 

  • Zhao W, Xie W, Le W, Beers DR, He Y, Henkel JS, Simpson EP, Yen AA, Xiao Q, Appel SH (2004) Activated microglia initiate motor neuron injury by a nitric oxide and glutamate-mediated mechanism. J Neuropathol Exp Neurol 63(9):964–977

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    Kenneth H. Clark & Clayton A. Wiley

  2. VA Pittsburgh Health Services, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Charles W. Bradberry

  3. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Charles W. Bradberry

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  1. Kenneth H. Clark
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  2. Clayton A. Wiley
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  3. Charles W. Bradberry
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Correspondence to Charles W. Bradberry.

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Clark, K.H., Wiley, C.A. & Bradberry, C.W. Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection. Neurotox Res 23, 174–188 (2013). https://doi.org/10.1007/s12640-012-9334-7

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  • DOI: https://doi.org/10.1007/s12640-012-9334-7

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