, 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



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.


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.


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.


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.


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.


Glucocorticoid receptors Mifepristone Sensitization Amphetamine Psychostimulant Mice Novelty 



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


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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

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