Journal of Neural Transmission

, Volume 107, Issue 10, pp 1229–1238 | Cite as

Enhancement of antipsychotic-like effects by combined treatment with the α1-adrenoceptor antagonist prazosin and the dopamine D2 receptor antagonist raclopride in rats

  • M.-L. Wadenberg
  • P. Hertel
  • R. Fernholm
  • K. Hygge Blakeman
  • S. Ahlenius
  • T. H. Svensson
Short Communication

Summary.

Blockade of central α1-adrenoceptors has been implicated as a possible factor contributing to the atypical antipsychotic profile of clozapine. Thus, in the present study we examined the effects of concomitant α1-adrenoceptor and dopamine D2 receptor blockade on conditioned avoidance response performance, as an index of antipsychotic-like activity, and on the induction of catalepsy, as a test for extrapyramidal side effect liability, in rats. It was found that pretreatment with the α1-adrenoceptor antagonist prazosin (0.2 mg kg−1 s.c.) caused an enhancement of a suppression of conditioned avoidance response in the presence of the dopamine D2 receptor antagonist raclopride (0.05–0.20 mg kg−1 s.c.). The effect was most prominent at a subthreshold dose of raclopride (0.05 mg kg−1). At these doses, prazosin or raclopride by themselves, or in combination, did not produce catalepsy. In addition, pretreatment with prazosin (0.2 mg kg−1 s.c.) did not alter the catalepsy produced by a higher dose of raclopride (1.0 mg kg−1 s.c.). It is suggested that, in the presence of low dopamine D2 receptor occupancy, additional α1-adrenoceptor blockade might improve antipsychotic efficacy, and thereby improve the therapeutic window with regard to parkinsonism.

Keywords: Conditioned avoidance, dopamine D2 receptors, α1-adrenoceptors, rat. 

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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • M.-L. Wadenberg
    • 1
  • P. Hertel
    • 1
  • R. Fernholm
    • 1
  • K. Hygge Blakeman
    • 1
  • S. Ahlenius
    • 1
  • T. H. Svensson
    • 1
  1. 1.Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Karolinska Institutet, Stockholm, SwedenSE

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