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Involvement of 5-HT1Areceptors in the anxiolytic action of S 14671 in the pigeon conflict test

Pharmacology Biochemistry and Behavior
Publication Date
DOI: 10.1016/0091-3057(94)00421-e
  • 5-Ht1Areceptor
  • Anxiety
  • Pigeon Conflict
  • S 14506
  • S 14671


Abstract In the pigeon conflict test of anxiety, the novel, high efficacy 5-HT 1A receptor ligand, S 14671, very potently [minimal effective dose (MED): 0.0025 mg/kg, IM] and markedly (maximal percentage increase relative to control: 17232%) increased punished responding. In analogy, its structural analogue, the 5-HT 1A receptor agonist, S 14506, equipotently, though less markedly, augmented punished responding (MED: 0.0025 mg/kg; maximal effect: 5557%). In contrast, the arylpiperazine 5-HT 1A receptor agonists, LY 165,163 and tandospirone, increased punished responding only at higher doses (MED: 0.16 and 0.63 mg/kg, respectively), and also with a lesser maximal effect (2065% and 3695%, respectively). Although S 14671 and S 14506 showed a 16-fold separation between doses, increasing punished and decreasing unpunished responding, respectively, this separation was only fourfold for LY 165,163 and tandospirone. The anticonflict activity of S 14671 (0.01 mg/kg) was significantly antagonised by the 5-HT 1A receptor antagonist, (−)-alprenolol (10 mg/kg), but not by combined treatment with the selective β 1 receptor antagonist, betaxolol, and the selective β 2 receptor antagonist, ICI 118,551. Further, a correlation analysis across each of the above agonists, as well as 8-OH-DPAT, buspirone, and (+)-flesinoxan, revealed a significant correlation for their relative potency in augmenting punished responding and their affinity for 5-HT 1A receptors in vitro ( r = +0.95, p < 0.001). It is concluded that S 14671 is an exceptionally potent and efficacious ligand in the pigeon conflict test and that its anxiolytic action reflects the activation of 5-HT 1A receptors.

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