Psychopharmacology

, Volume 230, Issue 4, pp 547–556 | Cite as

Mifepristone treatment affects the response to repeated amphetamine injections, but does not attenuate the expression of sensitization

  • Rixt van der Veen
  • Marieke C. S. Boshuizen
  • E. Ronald de Kloet
Original Investigation

Abstract

Rationale

Glucocorticoid hormones facilitate sensitization to repeated administration of psychostimulants, an effect that is mediated by glucocorticoid receptors (GRs). It is still unclear, however, at which stage of psychomotor sensitization are stress and GR-mediated effects involved.

Objectives

In the present study, we have tested the hypothesis that GR-mediated effects during the phase of repeated amphetamine injections play a crucial role in the long-term expression of sensitization. For this purpose, we used DBA/2 mice, an inbred strain commonly used for the study of stress effects on psychostimulant sensitization.

Methods

Animals were treated with the GR antagonist mifepristone (200 mg/kg) at 2.5 h before each daily injection of amphetamine (2.5 mg/kg) or saline in a 5-day protocol. The amphetamine or saline injections were given in the home or a novel context. This was followed by a 2.5-week withdrawal period, without any drug delivery. Following the withdrawal period, two low-dose amphetamine challenges (1.25 mg/kg) were given subsequently, without additional mifepristone.

Results

The animals receiving amphetamine in the novel context showed a higher expression of sensitization at challenge as compared to those in the home condition. Mifepristone treatment influenced locomotor response to repeated amphetamine injections, but this effect during the initial phase did not affect the expression of sensitization after a withdrawal period.

Conclusion

Our results indicate that GR-related processes during the initial phase of sensitization are involved in, but not crucial for, the development of long-term sensitization.

Keywords

Glucocorticoid receptors Mifepristone Sensitization Amphetamine Psychostimulant Mice Novelty 

Notes

Acknowledgments

This work was supported by TI Pharma T5-209. ERdK was supported by the Royal Netherlands Academy of Science.

References

  1. Badiani A, Browman KE, Robinson TE (1995a) Influence of novel versus home environments on sensitization to the psychomotor stimulant effects of cocaine and amphetamine. Brain Res 674:291–298PubMedCrossRefGoogle Scholar
  2. Badiani A, Cabib S, Puglisi-Allegra S (1992) Chronic stress induces strain-dependent sensitization to the behavioral effects of amphetamine in the mouse. Pharmacol Biochem Behav 43:53–60PubMedCrossRefGoogle Scholar
  3. Badiani A, Morano MI, Akil H, Robinson TE (1995b) Circulating adrenal hormones are not necessary for the development of sensitization to the psychomotor activating effects of amphetamine. Brain Res 673:13–24PubMedCrossRefGoogle Scholar
  4. Badiani A, Robinson TE (2004) Drug-induced neurobehavioral plasticity: the role of environmental context. Behav Pharmacol 15:327–339PubMedCrossRefGoogle Scholar
  5. Barik J, Parnaudeau S, Saint Amaux AL, Guiard BP, Golib Dzib JF, Bocquet O, Bailly A, Benecke A, Tronche F (2010) Glucocorticoid receptors in dopaminoceptive neurons, key for cocaine, are dispensable for molecular and behavioral morphine responses. Biol Psychiatry 68:231–239PubMedCrossRefGoogle Scholar
  6. Cabib S, Algeri S, Perego C, Puglisi-Allegra S (1990) Behavioral and biochemical changes monitored in two inbred strains of mice during exploration of an unfamiliar environment. Physiol Behav 47:749–753PubMedCrossRefGoogle Scholar
  7. Cabib S, Orsini C, Le Moal M, Piazza PV (2000) Abolition and reversal of strain differences in behavioral responses to drugs of abuse after a brief experience. Science 289:463–465PubMedCrossRefGoogle Scholar
  8. Conversi D, Bonito-Oliva A, Orsini C, Cabib S (2006) Habituation to the test cage influences amphetamine-induced locomotion and Fos expression and increases FosB/DeltaFosB-like immunoreactivity in mice. Neuroscience 141:597–605PubMedCrossRefGoogle Scholar
  9. Dalm, S. (2012) Towards a mouse model of depression: a psychoneuroendocrine approach. Thesis/Dissertation, Leiden UniversityGoogle Scholar
  10. Dalm S, Brinks V, van der Mark MH, de Kloet ER, Oitzl MS (2008) Non-invasive stress-free application of glucocorticoid ligands in mice. J Neurosci Methods 170:77–84PubMedCrossRefGoogle Scholar
  11. de Jong IEM, de Kloet ER (2009) Critical time-window for the actions of adrenal glucocorticoids in behavioural sensitisation to cocaine. Eur J Pharmacol 604:66–73PubMedCrossRefGoogle Scholar
  12. de Jong IEM, Oitzl MS, de Kloet ER (2007) Adrenalectomy prevents behavioural sensitisation of mice to cocaine in a genotype-dependent manner. Behav Brain Res 177:329–339PubMedCrossRefGoogle Scholar
  13. de Jong IEM, Steenbergen PJ, de Kloet ER (2009) Behavioral sensitization to cocaine: cooperation between glucocorticoids and epinephrine. Psychopharmacology (Berl) 204:693–703CrossRefGoogle Scholar
  14. de Kloet ER, de Jong IEM, Oitzl MS (2008) Neuropharmacology of glucocorticoids: focus on emotion, cognition and cocaine. Eur J Pharmacol 585:473–482PubMedCrossRefGoogle Scholar
  15. de Kloet ER, Joels M, Holsboer F (2005) Stress and the brain: from adaptation to disease. Nat Rev Neurosci 6:463–475PubMedCrossRefGoogle Scholar
  16. De Vries TJ, Schoffelmeer AN, Tjon GH, Nestby P, Mulder AH, Vanderschuren LJ (1996) Mifepristone prevents the expression of long-term behavioural sensitization to amphetamine. Eur J Pharmacol 307:R3–R4PubMedCrossRefGoogle Scholar
  17. Deroche-Gamonet V, Sillaber I, Aouizerate B, Izawa R, Jaber M, Ghozland S, Kellendonk C, Le Moal M, Spanagel R, Schutz G, Tronche F, Piazza PV (2003) The glucocorticoid receptor as a potential target to reduce cocaine abuse. J Neurosci 23:4785–4790PubMedGoogle Scholar
  18. Dong Z, Han H, Wang M, Xu L, Hao W, Cao J (2006) Morphine conditioned place preference depends on glucocorticoid receptors in both hippocampus and nucleus accumbens. Hippocampus 16:809–813PubMedCrossRefGoogle Scholar
  19. Fiancette JF, Balado E, Piazza PV, Deroche-Gamonet V (2010) Mifepristone and spironolactone differently alter cocaine intravenous self-administration and cocaine-induced locomotion in C57BL/6J mice. Addict Biol 15:81–87PubMedCrossRefGoogle Scholar
  20. Giardino WJ, Pastor R, Anacker AM, Spangler E, Cote DM, Li J, Stenzel-Poore MP, Phillips TJ, Ryabinin AE (2011) Dissection of corticotropin-releasing factor system involvement in locomotor sensitivity to methamphetamine. Genes Brain Behav 10:78–89PubMedCrossRefGoogle Scholar
  21. Marinelli M, Piazza PV (2002) Interaction between glucocorticoid hormones, stress and psychostimulant drugs. Eur J Neurosci 16:387–394PubMedCrossRefGoogle Scholar
  22. Oomen CA, Mayer JL, de Kloet ER, Joels M, Lucassen PJ (2007) Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress. Eur J Neurosci 26:3395–3401PubMedCrossRefGoogle Scholar
  23. Paulson PE, Camp DM, Robinson TE (1991) Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats. Psychopharmacology (Berl) 103:480–492CrossRefGoogle Scholar
  24. Pauly JR, Robinson SF, Collins AC (1993) Chronic corticosterone administration enhances behavioral sensitization to amphetamine in mice. Brain Res 620:195–202PubMedCrossRefGoogle Scholar
  25. Prasad BM, Ulibarri C, Kalivas PW, Sorg BA (1996) Effect of adrenalectomy on the initiation and expression of cocaine-induced sensitization. Psychopharmacology (Berl) 125:265–273CrossRefGoogle Scholar
  26. Przegalinski E, Filip M, Siwanowicz J, Nowak E (2000) Effect of adrenalectomy and corticosterone on cocaine-induced sensitization in rats. J Physiol Pharmacol 51:193–204PubMedGoogle Scholar
  27. Rivet JM, Stinus L, LeMoal M, Mormede P (1989) Behavioral sensitization to amphetamine is dependent on corticosteroid receptor activation. Brain Res 498:149–153PubMedCrossRefGoogle Scholar
  28. Shalev U, Erb S, Shaham Y (2010) Role of CRF and other neuropeptides in stress-induced reinstatement of drug seeking. Brain Res 1314:15–28PubMedCrossRefGoogle Scholar
  29. Tassin JP (2008) Uncoupling between noradrenergic and serotonergic neurons as a molecular basis of stable changes in behavior induced by repeated drugs of abuse. Biochem Pharmacol 75:85–97PubMedCrossRefGoogle Scholar
  30. van der Veen R, Koehl M, Abrous DN, de Kloet ER, Piazza PV, Deroche-Gamonet V (2008) Maternal environment influences cocaine intake in adulthood in a genotype-dependent manner. PLoS One 3:e2245PubMedCrossRefGoogle Scholar
  31. van der Veen R, Piazza PV, Deroche-Gamonet V (2007) Gene-environment interactions in vulnerability to cocaine intravenous self-administration: a brief social experience affects intake in DBA/2J but not in C57BL/6J mice. Psychopharmacology (Berl) 193:179–186CrossRefGoogle Scholar
  32. Vanderschuren LJ, Kalivas PW (2000) Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology (Berl) 151:99–120CrossRefGoogle Scholar
  33. Vezina P (2004) Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci Biobehav Rev 27:827–839PubMedCrossRefGoogle Scholar
  34. Vezina P, Leyton M (2009) Conditioned cues and the expression of stimulant sensitization in animals and humans. Neuropharmacology 56(Suppl 1):160–168PubMedCrossRefGoogle Scholar
  35. Wulsin AC, Herman JP, Solomon MB (2010) Mifepristone decreases depression-like behavior and modulates neuroendocrine and central hypothalamic-pituitary-adrenocortical axis responsiveness to stress. Psychoneuroendocrinology 35:1100–1112PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Rixt van der Veen
    • 1
    • 2
  • Marieke C. S. Boshuizen
    • 3
  • E. Ronald de Kloet
    • 1
  1. 1.Division of Medical PharmacologyLeiden Academy Center for Drug Research and Leiden University Medical CenterLeidenThe Netherlands
  2. 2.Centre for Child and Family StudiesLeiden UniversityLeidenThe Netherlands
  3. 3.Department of Medical BiochemistryUniversity of Amsterdam, Academic Medical CenterAmsterdamThe Netherlands

Personalised recommendations