Psychopharmacology

, Volume 203, Issue 4, pp 781–792

Sigma1 receptor antagonists determine the behavioral pattern of the methamphetamine-induced stereotypy in mice

  • J. Kitanaka
  • N. Kitanaka
  • T. Tatsuta
  • F. S. Hall
  • G. R. Uhl
  • K. Tanaka
  • N. Nishiyama
  • Y. Morita
  • M. Takemura
Original Investigation

DOI: 10.1007/s00213-008-1425-z

Cite this article as:
Kitanaka, J., Kitanaka, N., Tatsuta, T. et al. Psychopharmacology (2009) 203: 781. doi:10.1007/s00213-008-1425-z

Abstract

Objective

The effects of sigma receptor antagonists on methamphetamine (METH)-induced stereotypy have not been examined. We examined the effects of sigma antagonists on METH-induced stereotypy in mice.

Results

The administration of METH (10 mg/kg) to male ddY mice induced stereotyped behavior consisting of biting (90.1%), sniffing (4.2%), head bobbing (4.1%), and circling (1.7%) during an observation period of 1 h. Pretreatment of the mice with BMY 14802 (α-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazinebutanol; 1, 5, and 10 mg/kg), a non-specific sigma receptor antagonist, significantly increased METH-induced sniffing (19.2%, 30.5%, and 43.8% of total stereotypical behavior) but decreased biting (76.6%, 66.9%, and 49.3% of total stereotypical behavior) in a dose-dependent manner. This response was completely abolished by (+)-SKF 10,047 ([2S-(2α,6α,11R)]-1,2,3,4,5,6-hexahydro-6,11-dimethyl-3-(2-propenyl)-2,6-methano-3-benzazocin-8-ol; 4 and 10 mg/kg), a putative sigma1 receptor agonist, and partially by PB 28 (1-cyclohexyl-4-[3-(1,2,3,4-tetrahydro-5-methoxy-1-naphthalen-1-yl)-n-propyl]piperazine; 1 and 10 mg/kg), a putative sigma2 receptor agonist. The BMY 14802 action on METH-induced stereotypy was mimicked by BD 1047 (N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine; 10 mg/kg), a putative sigma1 receptor antagonist, but not by SM-21 ((±)-tropanyl 2-(4-chlorophenoxy)butanoate; 1 mg/kg), a putative sigma2 receptor antagonist. The BD 1047 effect on METH-induced stereotypy was also abolished completely by (+)-SKF 10,047 and partially by PB 28. The overall frequency of METH-induced stereotypical behavior was unchanged with these sigma receptor ligands, despite the alteration in particular behavioral patterns. The BMY 14802 action on METH-induced stereotypy was unaffected by pretreatment with centrally acting histamine H1 receptor antagonists (pyrilamine or ketotifen, 10 mg/kg), suggesting that these effects are independent of histamine H1 receptor signaling systems.

Conclusion

In summary, modulation of central sigma1 receptors alters the pattern of METH-induced stereotypy, producing a shift from stereotypical biting to stereotypical sniffing, without affecting the overall frequency of stereotypical behavior.

Keywords

MethamphetamineStereotypySniffingBitingBMY 14802Sigma ligandSigma receptor

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • J. Kitanaka
    • 1
  • N. Kitanaka
    • 1
  • T. Tatsuta
    • 2
  • F. S. Hall
    • 3
  • G. R. Uhl
    • 3
  • K. Tanaka
    • 4
  • N. Nishiyama
    • 4
  • Y. Morita
    • 2
  • M. Takemura
    • 1
  1. 1.Department of PharmacologyHyogo College of MedicineNishinomiyaJapan
  2. 2.Department of NeuropsychiatryHyogo College of MedicineNishinomiyaJapan
  3. 3.Molecular Neurobiology BranchNational Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, U.S. Department of Health and Human ServicesBaltimoreUSA
  4. 4.Division of Pharmacology, Department of Pharmacy, School of PharmacyHyogo University of Health SciencesKobeJapan