Psychopharmacology

, Volume 202, Issue 4, pp 673–687

Effects of the H3 receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions

  • Christian Brabant
  • Livia Alleva
  • Thierry Grisar
  • Etienne Quertemont
  • Bernard Lakaye
  • Hiroshi Ohtsu
  • Jian-Sheng Lin
  • Peter Jatlow
  • Marina R. Picciotto
  • Ezio Tirelli
Original Investigation

DOI: 10.1007/s00213-008-1345-y

Cite this article as:
Brabant, C., Alleva, L., Grisar, T. et al. Psychopharmacology (2009) 202: 673. doi:10.1007/s00213-008-1345-y

Abstract

Rationale

Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H3 receptor inverse agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice.

Materials and methods

We investigated whether immepip, a selective H3 agonist, could reverse the potentiating effects of thioperamide. Moreover, the non-imidazole H3 inverse agonist A-331440 was tested on the locomotor effects of cocaine. Using high-performance liquid chromatography with ultraviolet detection, cocaine plasma concentrations were measured to study potential drug–drug interactions between thioperamide and cocaine. Finally, thioperamide was tested on the locomotor effects of cocaine in histamine-deficient knockout mice in order to determine the contribution of histamine to the modulating effects of thioperamide.

Results

Thioperamide potentiated cocaine-induced hyperlocomotion in normal mice, and to a higher extent, in histamine-deficient knockout mice. A-331440 only slightly affected the locomotor effects of cocaine. Immepip did not alter cocaine-induced hyperactivity but significantly reduced the potentiating actions of thioperamide on cocaine’s effects. Finally, plasma cocaine concentrations were more elevated in mice treated with thioperamide than in mice that received cocaine alone.

Conclusions

The present results indicate that histamine released by thioperamide through the blockade of H3 autoreceptors is not involved in the ability of this compound to potentiate cocaine induced-hyperactivity. Our data suggest that thioperamide, at least at 10 mg/kg, increases cocaine-induced locomotion through the combination of pharmacokinetic effects and the blockade of H3 receptors located on non-histaminergic neurons.

Keywords

CocaineHistamineThioperamideImmepipA-331440H3 receptorLocomotionKnockout mouse

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Christian Brabant
    • 1
    • 2
    • 5
  • Livia Alleva
    • 1
  • Thierry Grisar
    • 2
  • Etienne Quertemont
    • 1
  • Bernard Lakaye
    • 2
  • Hiroshi Ohtsu
    • 3
  • Jian-Sheng Lin
    • 4
  • Peter Jatlow
    • 6
  • Marina R. Picciotto
    • 5
  • Ezio Tirelli
    • 1
  1. 1.Centre de Neurosciences Cognitives et Comportementales (CNCC)Université de LiègeLiègeBelgium
  2. 2.Centre de Recherche en Neurobiologie Cellulaire et Moléculaire (CNCM)Université de LiègeLiègeBelgium
  3. 3.Department of Quantum Science and Energy Engineering, School of EngineeringTohoku UniversitySendaiJapan
  4. 4.INSERM-U628, IFR19, Département de Médecine Expérimentale, Faculté de MédecineUniversité Claude BernardLyonFrance
  5. 5.Department of PsychiatryYale University School of MedicineNew HavenUSA
  6. 6.Department of Laboratory MedicineYale University School of MedicineNew HavenUSA