, Volume 97, Issue 3, pp 319–325 | Cite as

Behavioral and neurochemical effects of the serotonin (5-HT)1A receptor ligand spiroxatrine

  • J. E. Barrett
  • S. M. Hoffmann
  • S. N. Olmstead
  • M. J. Foust
  • C. Harrod
  • B. A. Weissman
Original Investigations


The effects of spiroxatrine, a putative antagonist with selectivity for the serotonin (5-HT)1A receptor, were compared with compounds believed to function as agonists at the 5-HT1A receptor. Schedule-controlled responding of pigeons was maintained under a multiple 30-response fixed-ratio (FR), 3-min fixed-interval (FI) schedule or under a schedule in which responding was suppressed by electric shock (“conflict” procedure). Under the multiple schedule, spiroxatrine (0.3–1.0 mg/kg) decreased FR responding but did not affect FI responding; responding was decreased in both schedule components at 3.0 mg/kg. When administered alone, buspirone, a compound believed to produce its anxiolytic effects through 5-HT1A agonist actions, produced effects similar to those of spiroxatrine; in combination, the two drugs produced greater effects than when either was administered alone. As with 5-HT1A agonists such as buspirone and 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) in the pigeon, spiroxatrine (0.01–1.0 mg/kg) increased punished responding. Spiroxatrine and buspirone were potent inhibitors of [3H]8-OH-DPAT binding to pigeon cerebral membranes with IC50 values in the nM range. Neurochemical analyses of metabolite changes produced by spiroxatrine in pigeon cerebrospinal fluid showed buspirone-like effects, with increases in MHPG, DOPAC and HVA at doses that decreased 5-HIAA levels. Spiroxatrine dose-dependently blocked the behavioral effects of the dopamine agonist piribedil indicating that, like buspirone, it also is a potent dopamine antagonist. Spiroxatrine most likely functions as an agonist at the 5-HT1A receptor. As with buspirone, however, spiroxatrine has a prominent dopamine antagonist component.

Key words

Spiroxatrine 8-OH-DPAT Serotonin 5-HT1A Buspirone Pigeon 


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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • J. E. Barrett
    • 1
  • S. M. Hoffmann
    • 1
  • S. N. Olmstead
    • 1
  • M. J. Foust
    • 1
  • C. Harrod
    • 1
  • B. A. Weissman
    • 2
  1. 1.Department of PsychiatryUniformed Services University of the Health SciencesBethesdaUSA
  2. 2.Department of PharmacologyIsrael Institute for Biological ResearchNess ZionaIsrael

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