Skip to main content
SpringerLink
Log in

Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Accumulating evidence suggested that glial cells are involved in synaptic plasticity and behavioral changes induced by drugs abuse. The role of these cells in maintenance and reinstatement of morphine (MRP) conditioned place preference (CPP) remains poorly characterized. The aim of present study was to investigate the direct role of glial cells in nucleus accumbens (NAc) in the maintenance and reinstatement of MRP-seeking behavior. CPP induced with injection of MRP (5 mg/kg, s.c. for 3 days), lasted for 7 days after cessation of MRP treatment and priming dose of MRP (1 mg/kg, s.c.) reinstated the extinguished MRP-induced CPP. The astrocyte-conditioned medium (ACM) and neuroglia conditioned medium (NCM) exposed to MRP (10 and 100 µM) have been microinjected into the NAc. Intra-NAc administration of ACM during extinction period failed to change the maintenance of MRP-CPP, but MRP 100-treated ACM could slightly increase the magnitude of reinstatement. In contrast to ACM, intra-NAc administration of MRP 100-treated NCM caused slower extinction by 3 days and significantly increased the magnitude of reinstatement. Our findings suggest the involvement of glial cells activation in the maintenance and reinstatement of MRP-seeking behaviors, and provides new evidence that these cells might be a potential target for the treatment of MRP addiction.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ACM:

Astrocyte-conditioned medium

BDNF:

Brain-derived neurotrophic factor

CG:

Cingulate cortex

CNS:

Central nervous system

CREB:

cAMP response element-binding protein

CPP:

Conditioned place preference

DMEM:

Dulbecco’s modified Eagle’s medium

GFAP:

Glial fibrillary acidic

iNOS:

Inducible nitric oxide synthase

METH:

Methamphetamine

mPFC:

Medial prefrontal cortex

MRP:

Morphine

MRP10-ACM:

Morphine (10 µM, 3 days)-treated astrocyte conditioned medium

MRP100-ACM:

Morphine (100 µM, 3 days)-treated astrocyte conditioned medium

MRP10-NCM:

Morphine (10 µM, 3 days)-treated neuroglia conditioned medium

MRP100-NCM:

Morphine (100 µM, 3 days)-treated neuroglia conditioned medium

NAc:

Nucleus accumbens

NCM:

Neuroglia conditioned medium

NO:

Nitric oxide

PBS:

Phosphate-buffered saline

TNF-α:

Tumor necrosis factor-α

VTA:

Ventral tegmental area

References

  1. Van Ree JM, Gerrits MA, Vanderschuren LJ (1999) Opioids, reward and addiction: an encounter of biology, psychology, and medicine. Pharmacol Rev 51:341–396

    PubMed  Google Scholar 

  2. Veilleux JC, Colvin PJ, Anderson J, York C, Heinz AJ (2009) A review of opioid dependence treatment: pharmacological and psychosocial interventions to treat opioid addiction. Clin Psychol Rev 30:155–166

    Article  PubMed  Google Scholar 

  3. Miguel-Hidalgo JJ (2009) The role of glial cells in drug abuse. Curr Drug Abuse Rev 2:76–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Koob JF (2006) The neurobiology of addiction: a neuroadaptational view relevant for diagnosis. Addiction 101:23–30

    Article  PubMed  Google Scholar 

  5. Goodman A (2007) Neurobiology of addiction, An integrative review. Biochem Pharmacol 75:266–322

    Article  PubMed  Google Scholar 

  6. Nestler EJ (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. Aguilar MA, Rodriguez-Arias M, Minarro J (2009) Neurobiological mechanisms of the reinstatement of drug-conditioned place preference. Brain Res Rev 59:253–277

    Article  PubMed  Google Scholar 

  9. DeLeo JA, Colburn RW (1999) Cytokines and pain. In: Watkins LR, Maier SF (eds) Proinflammatory cytokines and glial cells: their role in neuropathic pain. Springer, pp 159–181

  10. Vesce S, Bezzi P, Volterra A (2001) Synaptic transmission with the glia. Physiology 16:178–184

    CAS  Google Scholar 

  11. Kovács KJ (2012) Microglia and drug-induced plasticity in reward-related neuronal circuits. Front Mol Neurosci 5:1–3

    Article  Google Scholar 

  12. Bohn MC (2004) Motoneurons crave glial cell line-derived neurotrophic factor. Ex Neurol 190:263–275

    Article  CAS  Google Scholar 

  13. Fellin T, Carmignoto G (2004) Neurone-to-astrocyte signalling in the brain represents a distinct multifunctional unit. J Physiol 559:3–15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Narita M, Miyatake M, Narita M, Shibasaki M, Shindo K, Nakamura A, Kuzumaki N, Nagumo Y, Suzuki T (2006) Direct evidence of astrocytic modulation in the development of rewarding effects induced by drugs of abuse. Neuropsychopharmacology 31:2476–2488

    Article  CAS  PubMed  Google Scholar 

  15. Zhang X-Q, Cui Y, Cui Y, Chen Y, Na X-D, Chen F-Y, Wei X-H, Li Y-Y, Liu X-G, Xin W-J (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  CAS  PubMed  Google Scholar 

  16. Dong Y, Benveniste EN (2001) Immune function of astrocytes. Glia 36:180–190

    Article  CAS  PubMed  Google Scholar 

  17. Vijayaraghavan S (2009) Glial–neuronal interactions—implications for plasticity and drug addiction. AAPS J 11:123–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Song P, Zhao Z-Q (2001) The involvement of glial cells in the development of morphine tolerance. Neurosci Res 39:281–286

    Article  CAS  PubMed  Google Scholar 

  19. Narita M, Suzuki M, Kuzumaki N, Miyatake M, Suzuki T (2008) Implication of activated astrocytes in the development of drug dependence. Ann N Y Acad Sci 1141:96–104

    Article  CAS  PubMed  Google Scholar 

  20. Haydon PG, Blendy J, Moss SJ, Jackson FR (2009) Astrocytic control of synaptic transmission and plasticity: a target for drugs of abuse? Neuropharmacology 56:83–90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Beitner-Johnson D, Guitart X, Nestler EJ (1993) Glial fibrillary acidic protein and the mesolimbic dopamine system: regulation by chronic morphine and Lewis–Fischer strain differences in the rat ventral tegmental area. J Neurochem 61:1766–1773

    Article  CAS  PubMed  Google Scholar 

  22. Narita M, Miyatake M, Shibasaki M, Tsuda M, Koizumi S, Narita M, Yajima Y, Inoue K, Suzuki T (2005) Long-lasting change in brain dynamics induced by methamphetamine: enhancement of protein kinase C-dependent astrocytic response and behavioral sensitization. J Neurochem 93:1383–1392

    Article  CAS  PubMed  Google Scholar 

  23. Hutchinson MR, Northcutt AL, Chao LW, Kearney JJ, Zhang Y, Berkelhammer DL, Loram LC, Rozeske RR, Bland ST, Maier SF (2008) Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia. Brain Behav Immun 22:1248–1256

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Attarzadeh-Yazdi G, Arezoomandan R, Haghparast A (2014) Minocycline, an antibiotic with inhibitory effect on microglial activation, attenuates the maintenance and reinstatement of methamphetamine-seeking behavior in rat. Neuropsychopharmacol Biol Psychiatry 53:142–148

    Article  CAS  Google Scholar 

  25. Arezoomandan R, Haghparast A (2015) Administration of the glial cell modulator, minocycline, in the nucleus accumbens attenuated the maintenance and reinstatement of morphine-seeking behavior. Can J Physiol Pharmacol. doi:10.1139/cjpp-2015-0209

    PubMed  Google Scholar 

  26. Skaper SD, Argentini C, Barbierato M (2012) Culture of neonatal rodent microglia, astrocytes, and oligodendrocytes from cortex and spinal cord. Methods Mol Biol 846:67–77

    Article  CAS  PubMed  Google Scholar 

  27. Paxinos G, Watson C (2006) The rat brain in stereotaxic coordinates: hard cover edition. Academic Press, San Diego, pp 62–65

    Google Scholar 

  28. Riahi E, Khodagholi F, Haghparast A (2013) Role of dorsal hippocampal orexin-1 receptors in associating morphine reward with contextual stimuli. Behav Pharmacol 24:237–248

    Article  CAS  PubMed  Google Scholar 

  29. Cooper ZD, Jones JD, Comer SD (2012) Glial modulators: a novel pharmacological approach to altering the behavioral effects of abused substances. Expert Opin Investig Drug 21:169–178

    Article  CAS  Google Scholar 

  30. Mennicken F, Maki R, de Souza EB, Quirion R (1999) Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning. Trends Pharmacol Sci 20:73–78

    Article  CAS  PubMed  Google Scholar 

  31. Färber K, Kettenmann H (2005) Physiology of microglial cells. Brain Res Rev 48:133–143

    Article  PubMed  Google Scholar 

  32. Takayama N, Ueda H (2005) Morphine-induced chemotaxis and brain-derived neurotrophic factor expression in microglia. J Neurosci 25:430–435

    Article  CAS  PubMed  Google Scholar 

  33. Langmann T (2007) Microglia activation in retinal degeneration. J Leukoc Biol 81:1345–1351

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  35. 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  CAS  PubMed  PubMed Central  Google Scholar 

  36. Thomas DM, Dowgiert J, Geddes TJ, Francescutti-Verbeem D, Liu X, Kuhn DM (2004) Microglial activation is a pharmacologically specific marker for the neurotoxic amphetamines. Neurosci Lett 367:349–354

    Article  CAS  PubMed  Google Scholar 

  37. Shaw-Lutchman TZBM, Wallace T, Gilden L, Zachariou V, Impey S, Duman RS, Storm D, Nestler EJ (2002) Regional and cellular mapping of cAMP response element-mediated transcription during naltrexone-precipitated morphine withdrawal. J Neurosci 22:3663–3672

    CAS  PubMed  Google Scholar 

  38. Ghitza UE, Zhai H, Wu P, Airavaara M, Shaham Y, Lu L (2010) Role of BDNF and GDNF in drug reward and relapse: a review. Neurosci Biobehav Rev 35:157–171

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Horger BA, Iyasere CA, Berhow MT, Messer CJ, Nestler EJ, Taylor JR (1999) Enhancement of locomotor activity and conditioned reward to cocaine by brain-derived neurotrophic factor. J Neurosci 19:4110–4122

    CAS  PubMed  Google Scholar 

  40. Niwa M, Nitta A, Yamada K, Nabeshima T (2007) The roles of glial cell line-derived neurotrophic factor, tumor necrosis factor-. ALPHA., and an inducer of these factors in drug dependence. J Pharmacol Sci 104:116–121

    Article  CAS  PubMed  Google Scholar 

  41. Nandi J, Saud B, Zinkievich JM, Z-j Yang, Levine RA (2010) TNF-α modulates iNOS expression in an experimental rat model of indomethacin-induced jejunoileitis. Mol Cell Biochem 336:17–24

    Article  CAS  PubMed  Google Scholar 

  42. Pudiak CM, Bozarth MA (1993) L-NAME and MK-801 attenuate sensitization to the locomotor-stimulating effect of cocaine. Life Sci 53:1517–1524

    Article  CAS  PubMed  Google Scholar 

  43. Gholami A, Zarrindast M-R, Sahraei H, Haerri-Rohani A (2003) Nitric oxide within the ventral tegmental area is involved in mediating morphine reward. Eur J Pharmacol 458:119–128

    Article  CAS  PubMed  Google Scholar 

  44. Berhow MT, Hiroi N, Kobierski LA, Hyman SE, Nestler EJ (1996) Influence of cocaine on the JAK–STAT pathway in the mesolimbic dopamine system. J Neurosci 16:8019–8026

    CAS  PubMed  Google Scholar 

  45. Hebert MA, O’Callaghan JP (2000) Protein phosphorylation cascades associated with methamphetamine-induced glial activation. Ann N Y Acad Sci 914:238–262

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was carried out as part of a Ph.D. student thesis project in Shahid Beheshti University of Medical Sciences. The authors would like to thank Abbas Ali Aghaei for his constructive comments. This work was supported by the Grant (no. 92-261-A) from the Neuroscience Research Center of Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Author information

Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, P.O. Box 19615-1178, Tehran, Iran

    Reza Arezoomandan, Fariba Khodagholi & Abbas Haghparast

Authors
  1. Reza Arezoomandan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fariba Khodagholi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abbas Haghparast
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abbas Haghparast.

Ethics declarations

Conflict of interest

There are no conflicts of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 152 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arezoomandan, R., Khodagholi, F. & Haghparast, A. Administration of the Glial Condition Medium in the Nucleus Accumbens Prolong Maintenance and Intensify Reinstatement of Morphine-Seeking Behavior. Neurochem Res 41, 855–868 (2016). https://doi.org/10.1007/s11064-015-1762-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-015-1762-3

Keywords

Search

Navigation