Skip to main content
SpringerLink
Log in

Drug Addiction

  • Chapter
  • First Online:
Microglia in Health and Disease

Abstract

Drug addiction is a pervasive worldwide problem characterized by compulsive drug use that continues despite negative consequences and treatment attempts. Historically, the biological basis of drug addiction has focused principally on neuronal activity. However, despite their pivotal role in the underlying pathology of drug addiction, neurons are not the only central nervous system (CNS) component involved. The role of additional cell types, especially the CNS immunocompetent microglial cells, in the development of tolerance and related neuroplastic changes during drug taking, addiction, and withdrawal is also emerging. Within this perspective, this chapter reviews the roles of microglial cells in several aspects of drug addiction and its behavioural consequences, including reward, tolerance, dependence, and withdrawal. The cellular and molecular mechanisms which are particularly recruited will be emphasized. Lastly, we will also summarize the development of pharmacological modulators of microglial activation that offer novel treatment strategies and highlight the need to better understand the roles of microglia in the context of drug addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agrawal RG, Hewetson A, George CM et al (2011) Minocycline reduces ethanol drinking. Brain Behav Immun 25(Suppl 1):S165–S169

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Alfonso-Loeches S, Pascual-Lucas M, Blanco AM et al (2010) Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage. J Neurosci 30:8285–8295

    Article  PubMed  CAS  Google Scholar 

  • Bastos LF, de Oliveira AC, Watkins LR et al (2012) Tetracyclines and pain. Naunyn Schmiedebergs Arch Pharmacol 385:225–241

    Article  PubMed  CAS  Google Scholar 

  • Beardsley PM, Shelton KL, Hendrick E et al (2010) The glial cell modulator and phosphodiesterase inhibitor, AV411 (ibudilast), attenuates prime- and stress-induced methamphetamine relapse. Eur J Pharmacol 637:102–108

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Beattie EC, Stellwagen D, Morishita W et al (2002) Control of synaptic strength by glial TNFalpha. Science 295:2282–2285

    Article  PubMed  CAS  Google Scholar 

  • Belujon P, Grace AA (2011) Hippocampus, amygdala, and stress: interacting systems that affect susceptibility to addiction. Ann N Y Acad Sci 1216:114–121

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Bernardi RE, Lattal KM, Berger SP (2006) Postretrieval propranolol disrupts a cocaine conditioned place preference. Neuroreport 17:1443–1447

    Article  PubMed  CAS  Google Scholar 

  • Brundula V, Rewcastle NB, Metz LM et al (2002) Targeting leukocyte MMPs and transmigration: minocycline as a potential therapy for multiple sclerosis. Brain 125:1297–1308

    Article  PubMed  Google Scholar 

  • Bsibsi M, Ravid R, Gveric D et al (2002) Broad expression of Toll-like receptors in the human central nervous system. J Neuropathol Exp Neurol 61:1013–1021

    PubMed  CAS  Google Scholar 

  • Burns LH, Wang HY (2010) PTI-609: a novel analgesic that binds filamin A to control opioid signaling. Recent Pat CNS Drug Discov 5:210–220

    Article  PubMed  CAS  Google Scholar 

  • Ciraulo DA, Sarid-Segal O, Knapp CM et al (2005) Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence. Addiction 100(Suppl 1):12–22

    Article  PubMed  Google Scholar 

  • Coller JK, Hutchinson MR (2012) Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence. Pharmacol Ther 134:219–245

    Article  PubMed  CAS  Google Scholar 

  • Cooper ZD, Truong YN, Shi YG et al (2008) Morphine deprivation increases self-administration of the fast- and short-acting mu-opioid receptor agonist remifentanil in the rat. J Pharmacol Exp Ther 326:920–929

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • De A, Krueger JM, Simasko SM (2003) Tumor necrosis factor alpha increases cytosolic calcium responses to AMPA and KCl in primary cultures of rat hippocampal neurons. Brain Res 981:133–142

    Article  PubMed  CAS  Google Scholar 

  • Diogenes A, Ferraz CC, Akopian AN et al (2011) LPS sensitizes TRPV1 via activation of TLR4 in trigeminal sensory neurons. J Dent Res 90:759–764

    Article  PubMed  CAS  Google Scholar 

  • Domercq M, Vazquez-Villoldo N, Matute C (2013) Neurotransmitter signaling in the pathophysiology of microglia. Front Cell Neurosci 7:49

    PubMed  CAS  PubMed Central  Google Scholar 

  • Dutta K, Mishra MK, Nazmi A et al (2010) Minocycline differentially modulates macrophage mediated peripheral immune response following Japanese encephalitis virus infection. Immunobiology 215:884–893

    Article  PubMed  CAS  Google Scholar 

  • Espey MG, Chernyshev ON, Reinhard JF Jr et al (1997) Activated human microglia produce the excitotoxin quinolinic acid. Neuroreport 8:431–434

    Article  PubMed  CAS  Google Scholar 

  • Fan Y, Niu H, Rizak JD et al (2012) Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference, and delays morphine extinction in rats. Neurosci Bull 28:567–576

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Lizarbe S, Pascual M, Guerri C (2009) Critical role of TLR4 response in the activation of microglia induced by ethanol. J Immunol 183:4733–4744

    Article  PubMed  CAS  Google Scholar 

  • Fernandez-Lizarbe S, Montesinos J, Guerri C (2013) Ethanol induces TLR4/TLR2 association, triggering an inflammatory response in microglial cells. J Neurochem 126:261–273

    Article  PubMed  CAS  Google Scholar 

  • Ferraz CC, Henry MA, Hargreaves KM et al (2011) Lipopolysaccharide from Porphyromonas gingivalis sensitizes capsaicin-sensitive nociceptors. J Endod 37:45–48

    Article  PubMed  PubMed Central  Google Scholar 

  • Goldstein RZ, Volkow ND (2002) Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry 159:1642–1652

    Article  PubMed  PubMed Central  Google Scholar 

  • Graeber MB (2010) Changing face of microglia. Science 330:783–788

    Article  PubMed  CAS  Google Scholar 

  • Groenewegen HJ, Vermeulen-Van der Zee E, te Kortschot A et al (1987) Organization of the projections from the subiculum to the ventral striatum in the rat. A study using anterograde transport of Phaseolus vulgaris leucoagglutinin. Neuroscience 23:103–120

    Article  PubMed  CAS  Google Scholar 

  • Guo RX, Zhang M, Liu W et al (2009) NMDA receptors are involved in upstream of the spinal JNK activation in morphine antinociceptive tolerance. Neurosci Lett 467:95–99

    Article  PubMed  CAS  Google Scholar 

  • Habibi-Asl B, Hassanzadeh K, Charkhpour M (2009) Central administration of minocycline and riluzole prevents morphine-induced tolerance in rats. Anesth Analg 109:936–942

    Article  PubMed  CAS  Google Scholar 

  • Hameed H, Hameed M, Christo PJ (2010) The effect of morphine on glial cells as a potential therapeutic target for pharmacological development of analgesic drugs. Curr Pain Headache Rep 14:96–104

    Article  PubMed  Google Scholar 

  • He J, Crews FT (2008) Increased MCP-1 and microglia in various regions of the human alcoholic brain. Exp Neurol 210:349–358

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Herman JP, Mueller NK (2006) Role of the ventral subiculum in stress integration. Behav Brain Res 174:215–224

    Article  PubMed  CAS  Google Scholar 

  • Hermann GE, Rogers RC, Bresnahan JC et al (2001) Tumor necrosis factor-alpha induces cFOS and strongly potentiates glutamate-mediated cell death in the rat spinal cord. Neurobiol Dis 8:590–599

    Article  PubMed  CAS  Google Scholar 

  • Horvath RJ, DeLeo JA (2009) Morphine enhances microglial migration through modulation of P2X4 receptor signaling. J Neurosci 29:998–1005

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Horvath RJ, Romero-Sandoval EA, De Leo JA (2010) Inhibition of microglial P2X4 receptors attenuates morphine tolerance, Iba1, GFAP and mu opioid receptor protein expression while enhancing perivascular microglial ED2. Pain 150:401–413

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hutchinson MR, Bland ST, Johnson KW et al (2007) Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward. Scientific World Journal 7:98–111

    Article  PubMed  Google Scholar 

  • Hutchinson MR, Zhang Y, Brown K et al (2008) Non-stereoselective reversal of neuropathic pain by naloxone and naltrexone: involvement of toll-like receptor 4 (TLR4). Eur J Neurosci 28:20–29

    Article  PubMed  PubMed Central  Google Scholar 

  • Hutchinson MR, Lewis SS, Coats BD et al (2009) Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast). Brain Behav Immun 23:240–250

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hutchinson MR, Lewis SS, Coats BD et al (2010a) Possible involvement of toll-like receptor 4/myeloid differentiation factor-2 activity of opioid inactive isomers causes spinal proinflammation and related behavioral consequences. Neuroscience 167:880–893

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hutchinson MR, Zhang Y, Shridhar M et al (2010b) Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun 24:83–95

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hutchinson MR, Shavit Y, Grace PM et al (2011) Exploring the neuroimmunopharmacology of opioids: an integrative review of mechanisms of central immune signaling and their implications for opioid analgesia. Pharmacol Rev 63:772–810

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Hutchinson MR, Northcutt AL, Hiranita T et al (2012) Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci 32:11187–11200

    Article  PubMed  CAS  PubMed Central  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 

  • Ikemoto S, Panksepp J (1999) The role of nucleus accumbens dopamine in motivated behavior: a unifying interpretation with special reference to reward-seeking. Brain Res Brain Res Rev 31:6–41

    Article  PubMed  CAS  Google Scholar 

  • Inoue K (2006) The function of microglia through purinergic receptors: neuropathic pain and cytokine release. Pharmacol Ther 109:210–226

    Article  PubMed  CAS  Google Scholar 

  • Ji K, Akgul G, Wollmuth LP et al (2013) Microglia actively regulate the number of functional synapses. PLoS One 8:e56293

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Juni A, Klein G, Pintar JE et al (2007) Nociception increases during opioid infusion in opioid receptor triple knock-out mice. Neuroscience 147:439–444

    Article  PubMed  CAS  Google Scholar 

  • Kaczmarek-Hajek K, Lorinczi E, Hausmann R et al (2012) Molecular and functional properties of P2X receptors–recent progress and persisting challenges. Purinergic Signal 8:375–417

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kaindl AM, Degos V, Peineau S et al (2012) Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain. Ann Neurol 72:536–549

    Article  PubMed  CAS  Google Scholar 

  • Kampman KM, Volpicelli JR, Mulvaney F et al (2001) Effectiveness of propranolol for cocaine dependence treatment may depend on cocaine withdrawal symptom severity. Drug Alcohol Depend 63:69–78

    Article  PubMed  CAS  Google Scholar 

  • Kest B, Mogil JS, Shamgar BE et al (1993) The NMDA receptor antagonist MK-801 protects against the development of morphine tolerance after intrathecal administration. Proc West Pharmacol Soc 36:307–310

    PubMed  CAS  Google Scholar 

  • Kettenmann H, Hanisch UK, Noda M et al (2011) Physiology of microglia. Physiol Rev 91:461–553

    Article  PubMed  CAS  Google Scholar 

  • Kettenmann H, Kirchhoff F, Verkhratsky A (2013) Microglia: new roles for the synaptic stripper. Neuron 77:10–18

    Article  PubMed  CAS  Google Scholar 

  • Kierdorf K, Erny D, Goldmann T et al (2013) Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci 16:273–280

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2009) Brain stress systems in the amygdala and addiction. Brain Res 1293:61–75

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Kovacs KJ (2012) Microglia and drug-induced plasticity in reward-related neuronal circuits. Front Mol Neurosci 5:74

    Article  PubMed  PubMed Central  Google Scholar 

  • Ledeboer A, Hutchinson MR, Watkins LR et al (2007) Ibudilast (AV-411). A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes. Expert Opin Investig Drugs 16:935–950

    Article  PubMed  CAS  Google Scholar 

  • Lehnardt S, Massillon L, Follett P et al (2003) Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci U S A 100:8514–8519

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lewis SS, Hutchinson MR, Zhang Y et al (2013) Glucuronic acid and the ethanol metabolite ethyl-glucuronide cause toll-like receptor 4 activation and enhanced pain. Brain Behav Immun 30:24–32

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Li Y, Ji A, Schäfer MK (2002) Toll-like receptor 4 is expressed by peptidergic presumed nociceptive neurons in rat dorsal root ganglion. Soc Neurosci Abstr 46:19

    Google Scholar 

  • Li YQ, Xue YX, He YY et al (2011) Inhibition of PKMzeta in nucleus accumbens core abolishes long-term drug reward memory. J Neurosci 31:5436–5446

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lodge DJ, Grace AA (2008) Amphetamine activation of hippocampal drive of mesolimbic dopamine neurons: a mechanism of behavioral sensitization. J Neurosci 28:7876–7882

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Lowry CA (2002) Functional subsets of serotonergic neurones: implications for control of the hypothalamic-pituitary-adrenal axis. J Neuroendocrinol 14:911–923

    Article  PubMed  CAS  Google Scholar 

  • McClain JA, Morris SA, Deeny MA et al (2011) Adolescent binge alcohol exposure induces long-lasting partial activation of microglia. Brain Behav Immun 25(Suppl 1):S120–S128

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Substance Abuse and Mental Health Services Administration (2012) Results from the 2011 National Survey on Drug Use and Health: Summary of National Findings, NSDUH Series H-44, HHS Publication No. (SMA) 12-4713. Rockville, MD

    Google Scholar 

  • Miguel-Hidalgo JJ (2009) The role of glial cells in drug abuse. Curr Drug Abuse Rev 2:72–82

    Article  PubMed  Google Scholar 

  • Miguel-Hidalgo JJ, Wei J, Andrew M et al (2002) Glia pathology in the prefrontal cortex in alcohol dependence with and without depressive symptoms. Biol Psychiatry 52:1121–1133

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Milligan ED, Watkins LR (2009) Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10:23–36

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Mishra BB, Mishra PK, Teale JM (2006) Expression and distribution of Toll-like receptors in the brain during murine neurocysticercosis. J Neuroimmunol 181:46–56

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Neumann H, Wekerle H (2013) Brain microglia: watchdogs with pedigree. Nat Neurosci 16:253–255

    Article  PubMed  CAS  Google Scholar 

  • Okun E, Griffioen KJ, Mattson MP (2011) Toll-like receptor signaling in neural plasticity and disease. Trends Neurosci 34:269–281

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Pandey SC (2012) TLR4-MyD88 signalling: a molecular target for alcohol actions. Br J Pharmacol 165:1316–1318

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Pascual M, Balino P, Alfonso-Loeches S et al (2011) Impact of TLR4 on behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage. Brain Behav Immun 25(Suppl 1):S80–S91

    Article  PubMed  CAS  Google Scholar 

  • Pascual O, Ben Achour S, Rostaing P et al (2012) Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc Natl Acad Sci U S A 109:E197–E205

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Reeve AJ, Patel S, Fox A et al (2000) Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur J Pain 4:247–257

    Article  PubMed  CAS  Google Scholar 

  • Saladin ME, Gray KM, McRae-Clark AL et al (2013) A double blind, placebo-controlled study of the effects of post-retrieval propranolol on reconsolidation of memory for craving and cue reactivity in cocaine dependent humans. Psychopharmacology (Berl) 226:721–737

    Article  CAS  Google Scholar 

  • Schwarz JM, Hutchinson MR, Bilbo SD (2011) Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression. J Neurosci 31:17835–17847

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Shu H, Hayashida M, Huang W et al (2008) The comparison of effects of processed Aconiti tuber, U50488H and MK-801 on the antinociceptive tolerance to morphine. J Ethnopharmacol 117:158–165

    Article  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Snider SE, Vunck SA, van den Oord EJ et al (2012) The glial cell modulators, ibudilast and its amino analog, AV1013, attenuate methamphetamine locomotor activity and its sensitization in mice. Eur J Pharmacol 679:75–80

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Snider SE, Hendrick ES, Beardsley PM (2013) Glial cell modulators attenuate methamphetamine self-administration in the rat. Eur J Pharmacol 701:124–130

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Stellwagen D, Beattie EC, Seo JY et al (2005) Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 25:3219–3228

    Article  PubMed  CAS  Google Scholar 

  • Szeto GL, Pomerantz JL, Graham DR et al (2011) Minocycline suppresses activation of nuclear factor of activated T cells 1 (NFAT1) in human CD4+ T cells. J Biol Chem 286:11275–11282

    Article  PubMed  CAS  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Tanaka KF, Kashima H, Suzuki H et al (2002) Existence of functional beta1- and beta2-adrenergic receptors on microglia. J Neurosci Res 70:232–237

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Tremblay ME, Majewska AK (2011) A role for microglia in synaptic plasticity? Commun Integr Biol 4:220–222

    Article  PubMed  PubMed Central  Google Scholar 

  • Tremblay ME, Stevens B, Sierra A et al (2011) The role of microglia in the healthy brain. J Neurosci 31:16064–16069

    Article  PubMed  CAS  Google Scholar 

  • Tsai RY, Chou KY, Shen CH et al (2012) Resveratrol regulates N-methyl-D-aspartate receptor expression and suppresses neuroinflammation in morphine-tolerant rats. Anesth Analg 115:944–952

    Article  PubMed  CAS  Google Scholar 

  • Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12:227–462

    Article  PubMed  CAS  Google Scholar 

  • Ueda H, Ueda M (2009) Mechanisms underlying morphine analgesic tolerance and dependence. Front Biosci 14:5260–5272

    Article  CAS  Google Scholar 

  • Wang J, Li J, Sheng X et al (2010) Beta-adrenoceptor mediated surgery-induced production of pro-inflammatory cytokines in rat microglia cells. J Neuroimmunol 223:77–83

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Loram LC, Ramos K et al (2012) Morphine activates neuroinflammation in a manner parallel to endotoxin. Proc Natl Acad Sci U S A 109:6325–6330

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wang X, Smith C, Yin H (2013) Targeting Toll-like receptors with small molecule agents. Chem Soc Rev 42:4859–4866

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Watkins LR, Hutchinson MR, Johnston IN et al (2005) Glia: novel counter-regulators of opioid analgesia. Trends Neurosci 28:661–669

    Article  PubMed  CAS  Google Scholar 

  • Watkins LR, Hutchinson MR, Rice KC et al (2009) The “toll” of opioid-induced glial activation: improving the clinical efficacy of opioids by targeting glia. Trends Pharmacol Sci 30:581–591

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wu HE, Sun HS, Cheng CW et al (2006) dextro-Naloxone or levo-naloxone reverses the attenuation of morphine antinociception induced by lipopolysaccharide in the mouse spinal cord via a non-opioid mechanism. Eur J Neurosci 24:2575–2580

    Article  PubMed  Google Scholar 

  • Wu HE, Hong JS, Tseng LF (2007) Stereoselective action of (+)-morphine over (−)-morphine in attenuating the (−)-morphine-produced antinociception via the naloxone-sensitive sigma receptor in the mouse. Eur J Pharmacol 571:145–151

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Wu Y, Lousberg EL, Moldenhauer LM et al (2012) Inhibiting the TLR4-MyD88 signalling cascade by genetic or pharmacological strategies reduces acute alcohol-induced sedation and motor impairment in mice. Br J Pharmacol 165:1319–1329

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Yoshikawa M, Suzumura A, Tamaru T et al (1999) Effects of phosphodiesterase inhibitors on cytokine production by microglia. Mult Scler 5:126–133

    Article  PubMed  CAS  Google Scholar 

  • Youn DH, Wang H, Jeong SJ (2008) Exogenous tumor necrosis factor-alpha rapidly alters synaptic and sensory transmission in the adult rat spinal cord dorsal horn. J Neurosci Res 86:2867–2875

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Kitaichi K, Fujimoto Y et al (2006) Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry 30:1381–1393

    Article  PubMed  CAS  Google Scholar 

  • Zhang XQ, Cui Y, Chen Y et al (2012) Activation of p38 signaling in the microglia in the nucleus accumbens contributes to the acquisition and maintenance of morphine-induced conditioned place preference. Brain Behav Immun 26:318–325

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, China

    Xiaohui Wang Ph.D.

  2. Department of Psychology and the Center for Neuroscience, Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO, USA

    Xiaohui Wang Ph.D.

  3. Department of Psychology and the Center for Neuroscience, University of Colorado at Boulder, Boulder, CO, USA

    Thomas A. Cochran B.A. & Linda R. Watkins Ph.D.

  4. Discipline of Physiology, School of Medical Sciences, University of Adelaide, Level 5, Medical School South, S508, Frome Road, Adelaide, SA, 5005, Australia

    Mark R. Hutchinson Ph.D.

  5. Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado at Boulder, Boulder, CO, USA

    Hang Yin Ph.D.

Authors
  1. Xiaohui Wang Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas A. Cochran B.A.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mark R. Hutchinson Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hang Yin Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Linda R. Watkins Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Linda R. Watkins Ph.D. .

Editor information

Editors and Affiliations

  1. Axe Neurosciences, Centre de recherche du, CHU de Québec, and Department of Molecular Medicine, Université Laval, Québec, Québec, Canada

    Marie-Ève Tremblay

  2. Achucarro Basque Center for Neuroscience, University of the Basque Country, EHU/UPV, Ikerbasque Foundation, Zamudio, Bizkaia, Spain

    Amanda Sierra

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Wang, X., Cochran, T.A., Hutchinson, M.R., Yin, H., Watkins, L.R. (2014). Drug Addiction. In: Tremblay, MÈ., Sierra, A. (eds) Microglia in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1429-6_12

Download citation

Publish with us

Policies and ethics

Search

Navigation