Pharmacological Interaction With the Sigma_1 (σ_1)-Receptor in the Acute Behavioral Effects of Antidepressants

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Author(s)

Abstract

Selective agonists of the sigma-1 (<I>σ</I><SUB>1</SUB>) ligand–operated chaperone protein, like igmesine or PRE-084, are antidepressants in preclinical depression models. <I>σ</I><SUB>1</SUB>-Protein activation may contribute to the antidepressant efficacy of drugs known to act as selective serotonin-reuptake inhibitors (SSRI) or noradrenaline reuptake inhibitors through direct or indirect involvement of the <I>σ</I><SUB>1</SUB>-receptor in the drug effect. We here compared antidepressant effects in two behavioral procedures, the forced swimming test (FST) and conditioned fear stress (CFS). The involvement of the <I>σ</I><SUB>1</SUB>-receptor was examined using a co-treatment with the <I>σ</I><SUB>1</SUB>-antagonist BD1047 or using <I>σ</I><SUB>1</SUB>-knockout (KO) mice. Igmesine but not PRE-084 decreased FST immobility. The SSRI fluoxetine and sertraline, but not fluvoxamine, and the tricyclic antidepressants imipramine, desipramine, and amitriptyline were also effective. Only the effect of igmesine was blocked by BD1047 or in <I>σ</I><SUB>1</SUB>-KO mice. Igmesine, PRE-084, fluvoxamine, and sertraline decreased the CFS immobility in a BD1047- and <I>σ</I><SUB>1</SUB>-KO–sensitive manner. Among tricyclics, only amitriptyline was effective and its effect was unaffected by BD1047 or in <I>σ</I><SUB>1</SUB>-KO mice. The behavioral effects induced by mixed <I>σ</I><SUB>1</SUB>-receptor/SSRI antidepressants, like fluvoxamine or sertraline, may therefore involve a non-selective action at both targets. Moreover, the CFS appears to more reliably uncover a <I>σ</I><SUB>1</SUB> pharmacological component in antidepressant screening.

Journal

  • Journal of Pharmacological Sciences

    Journal of Pharmacological Sciences 115(3), 279-292, 2011-03-20

    The Japanese Pharmacological Society

References:  58

Cited by:  1

Codes

  • NII Article ID (NAID)
    10029892412
  • NII NACSIS-CAT ID (NCID)
    AA11806667
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13478613
  • NDL Article ID
    11009965
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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