Skip to main content

Effects of Naltrexone and Acamprosate on Alcohol-Induced NGFI-A Expression in Mouse Brain

Neurochemical Research volume 33, pages 2062–2069 (2008)Cite this article

Abstract

In search for the substrate of naltrexone and acamprosate action on alcohol craving, we investigated the effects of ethanol alone and combined with naltrexone or acamprosate on expression of nerve growth factor-inducible clone A (NGFI-A; zif268). In Experiments 1 and 3, alcohol (2 g/kg) alone or in combination with naltrexone (15 mg/kg) or acamprosate (300 mg/kg) was injected intraperitoneally into mice. In Experiment 2, treatment was nor-BNI (0.5 mg/kg) to investigate whether the effect of naltrexone involved blockade of κ-opioid receptors. Both ethanol and naltrexone alone induced NGFI-A in the central amygdala, but not in several other areas; these effects were additive. However, acamprosate alone or in combination with ethanol had no effect on NGFI-A mRNA, while nor-BNI induced NGFI-A mRNA in the basolateral amygdala. The central amygdala appears to be an important target of both alcohol and naltrexone. Acamprosate may not share the site of action with naltrexone despite being used for the same therapeutic purpose.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. O’Brien CP (2005) Anticraving medications for relapse prevention: a possible new class of psychoactive medications. Am J Psychiatry 162:1423–1431

    PubMed  Article  Google Scholar 

  2. O’Malley SS, Froehlich JC (2003) Advances in the use of naltrexone: an integration of preclinical and clinical findings. Recent Dev Alcohol 16:217–245

    PubMed  Article  Google Scholar 

  3. Terenius L (1998) Rational treatment of addiction. Curr Opin Chem Biol 3:541–547

    Article  Google Scholar 

  4. Sinclair JD (2001) Evidence about the use of naltrexone and for different ways of using it in the treatment of alcoholism. Alcohol Alcohol 36:2–10

    PubMed  CAS  Google Scholar 

  5. Volpicelli JR (1987) Uncontrollable events and alcohol drinking. Br J Addict 82:381–392

    PubMed  Article  CAS  Google Scholar 

  6. Volpicelli JR, Watson NT, King AC, Sherman CE, O’Brien CP (1995) Effect of naltrexone on alcohol “high” in alcoholics. Am J Psychiatry 152:613–615

    PubMed  CAS  Google Scholar 

  7. Herz A (1997) Endogenous opioid systems and alcohol addiction. Psychopharmacology 129:99–111

    PubMed  Article  CAS  Google Scholar 

  8. Gestreau C, Le Guen S, Besson JM (2000) Is there tonic activity in the endogenous opioid systems? A c-Fos Study in the rat central nervous system after intravenous injection of naloxone or naloxone–methiodide. J Comp Neurol 427:285–301

    PubMed  Article  CAS  Google Scholar 

  9. Kelley AE (2004) Ventral striatal control of appetitive motivation: role in ingestive behavior and reward-related learning. Neurosci Biobehav Rev 27:765–776

    PubMed  Article  Google Scholar 

  10. De Witte P, Littleton J, Parot P, Koob G (2005) Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action. CNS Drugs 19:517–537

    PubMed  Article  Google Scholar 

  11. Le F, Wilce P, Cassady I, Hume D, Shanley B (1990) Acute administration of ethanol suppresses pentylenetetrazole-induced c-fos expression in rat brain. Neurosci Lett 120:271–274

    PubMed  Article  CAS  Google Scholar 

  12. Bachtell RK, Wang YM, Freeman P, Risinger FO, Ryabinin AE (1999) Alcohol drinking produces brain region-selective changes in expression of inducible transcription factors. Brain Res 847:157–165

    PubMed  Article  CAS  Google Scholar 

  13. Worley PF, Bhat RV, Baraban JM, Erickson CA, McNaughton BL, Barnes CA (1993) Thresholds for synaptic activation of transcription factors in hippocampus: correlation with long-term enhancement. J Neurosci 13:4776–4786

    PubMed  CAS  Google Scholar 

  14. Paxinos G, Franklin KBJ (2000) The mouse brain in stereotaxic coordinates, 2nd edn. Academic Press, San Diego

    Google Scholar 

  15. Kuzmin A, Johansson B (1999) Expression of c-fos, NGFI-A and secretogranin II mRNA in brain regions during initiation of cocaine self-administration in mice. Eur J Neurosci 11:3694–3700

    PubMed  Article  CAS  Google Scholar 

  16. Farivar R, Zangenehpour S, Chaudhuri A (2004) Cellular-resolution activity mapping of the brain using immediate-early gene expression. Front Biosci 9:104–109

    PubMed  Article  CAS  Google Scholar 

  17. Bachtell RK, Tsivkovskaia NO, Ryabinin AE (2002) Alcohol-induced c-Fos expression in the Edinger–Westphal nucleus: pharmacological and signal transduction mechanisms. J Pharmacol Exp Ther 302:516–524

    PubMed  Article  CAS  Google Scholar 

  18. Kolodziejska-Akiyama KM, Cha YM, Jiang Y, Loh HH, Chang SL (2005) Ethanol-induced FOS immunoreactivity in the brain of μ-opioid receptor knockout mice. Drug Alcohol Depend 80:161–168

    PubMed  Article  CAS  Google Scholar 

  19. Foster KL, McKay PF, Seyoum R, Milbourne D, Yin W, Sarma PVVS, Cook JM, June HL (2004) GABAA and opioid receptors of the central amygdala selectively regulate ethanol-maintained behaviors. Neuropsychopharmacology 29:269–284

    PubMed  Article  CAS  Google Scholar 

  20. Ueyama T, Ohya H, Yoshimura R, Senba E (1999) Effects of ethanol on the stress-induced expression of NGFI-A mRNA in the rat brain. Alcohol 18:171–176

    PubMed  Article  CAS  Google Scholar 

  21. Roberto M, Madamba SG, Stouffer DG, Parsons LH, Siggins GR (2004) Increased GABA release in the central amygdala of ethanol-dependent rats. J Neurosci 24:10159–10166

    PubMed  Article  CAS  Google Scholar 

  22. Nie Z, Schweitzer P, Roberts AJ, Madamba SG, Moore SD, Siggins GR (2004) Ethanol augments GABAergic transmission in the central amygdala via CRF1 receptors. Science 303:1512–1514

    PubMed  Article  CAS  Google Scholar 

  23. Chang SL, Patel NA, Romero AA (1995) Activation and desensitization of Fos immunoreactivity in the rat brain following ethanol administration. Brain Res 679:89–98

    PubMed  Article  CAS  Google Scholar 

  24. Morales M, Criado JR, Sanna PP, Henricksen SJ, Bloom FE (1998) Acute ethanol induces c-fos immunoreactivity in GABAergic neurons of the central nucleus of the amygdala. Brain Res 708:333–336

    Article  Google Scholar 

  25. Thiele TT, van Dijk G, Berstein IL (1997) Ethanol-induced c-fos expression in rat lines selected for low and high alcohol consumption. Brain Res 756:278–282

    PubMed  Article  CAS  Google Scholar 

  26. Hitzemann B, Hitzemann R (1997) Genetics, ethanol and the fos response: a comparison of the C57BL/6 J and DBA/2 J inbred mouse strains. Alcohol Clin Exp Res 21:1497–1507

    PubMed  CAS  Google Scholar 

  27. Cowen MS, Chen F, Lawrence AJ (2004) Neuropeptides: implications for alcoholism. J Neurochem 89:273–285

    PubMed  Article  CAS  Google Scholar 

  28. Glass MJ, Billington CJ, Levine AS (2000) Naltrexone administered to central nucleus of amygdala or PVN: neural dissociation of diet and energy. Am J Physiol Regul Integr Comp Physiol 279:R86–R92

    PubMed  CAS  Google Scholar 

  29. Knapska E, Kaczmarek L (2004) A gene for neuronal plasticity in the mammalian brain: Zif268/Egr-1/NGFI-A/Krox-24/TIS8/ZENK? Prog Neurobiol 74:183–211

    PubMed  Article  CAS  Google Scholar 

  30. Oswald LM, Wand GS (2004) Opioids and alcoholism. Physiol Behav 81:339–358

    PubMed  Article  CAS  Google Scholar 

  31. Worst TJ, Vrana KE (2005) Alcohol and gene expression in the central nervous system. Alcohol Alcohol 40:63–75

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Supported by AFA Insurance (Stockholm, Sweden), Thuring’s Foundation (Stockholm, Sweden) and Programa Ramón y Cajal. MG received a predoctoral FI scholarship from Generalitat de Catalunya.

Author information

Affiliations

  1. Department of Clinical Neuroscience, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden

    Jeanette Lindholm, Marc Guitart-Masip, Homa Hassankhali, Sara Landgren, Camille Nicoleau, Lars Terenius & Björn Johansson

  2. Medical Psychology Unit, Department of Psychiatry and Forensic Medicine, Institut de Neurociències, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain

    Marc Guitart-Masip & Lydia Giménez-Llort

  3. Department of Neuroscience, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden

    Sven Ove Ögren & Björn Johansson

  4. Department of Molecular Medicine and Surgery, Center for Molecular Medicine L8:00, Karolinska Institutet, Karolinska University Hospital Solna, 171 76, Stockholm, Sweden

    Björn Johansson

Authors
  1. Jeanette Lindholm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marc Guitart-Masip
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Homa Hassankhali
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara Landgren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Camille Nicoleau
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lydia Giménez-Llort
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lars Terenius
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sven Ove Ögren
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Björn Johansson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Björn Johansson.

Additional information

Special issue article in honor of Dr.Ji-Sheng Han.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lindholm, J., Guitart-Masip, M., Hassankhali, H. et al. Effects of Naltrexone and Acamprosate on Alcohol-Induced NGFI-A Expression in Mouse Brain. Neurochem Res 33, 2062–2069 (2008). https://doi.org/10.1007/s11064-008-9687-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-008-9687-8

Keywords

  • Acamprosate
  • Amygdala
  • Ethanol
  • Naltrexone
  • NGFI-A
  • zif268