Schreiber R, Brocco M, de Ladonchamps B L, Millan M J
Department of Psychopharmacology, Centre de Recherches de Croissy, France.
Pharmacol Biochem Behav. 1995 Jun-Jul;51(2-3):211-5. doi: 10.1016/0091-3057(94)00421-e.
In the pigeon conflict test of anxiety, the novel, high efficacy 5-HT1A 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-HT1A receptor agonist, S 14506, equipotently, though less markedly, augmented punished responding (MED: 0.0025 mg/kg; maximal effect: 5557%). In contrast, the arylpiperazine 5-HT1A 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-HT1A receptor antagonist, (-)-alprenolol (10 mg/kg), but not by combined treatment with the selective beta 1 receptor antagonist, betaxolol, and the selective beta 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-HT1A 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-HT1A receptors.
在鸽子焦虑冲突试验中，新型高效5-羟色胺1A受体配体S 14671非常强效（最小有效剂量（MED）：0.0025毫克/千克，肌肉注射）且显著（相对于对照组的最大百分比增加：17232%）增加受罚反应。类似地，其结构类似物5-羟色胺1A受体激动剂S 14506同等效力，但作用不太显著，增强了受罚反应（MED：0.0025毫克/千克；最大效应：5557%）。相比之下，芳基哌嗪5-羟色胺1A受体激动剂LY 165163和坦度螺酮仅在较高剂量时（MED分别为0.16和0.63毫克/千克）增加受罚反应，且最大效应较小（分别为2065%和3695%）。尽管S 14671和S 14506在剂量上有16倍的差异，分别增加受罚反应和减少未受罚反应，但LY 165163和坦度螺酮的这种差异仅为四倍。S 14671（0.01毫克/千克）的抗冲突活性被5-羟色胺1A受体拮抗剂（-）-阿普洛尔（10毫克/千克）显著拮抗，但与选择性β1受体拮抗剂倍他洛尔和选择性β2受体拮抗剂ICI 118551联合治疗时未被拮抗。此外，对上述每种激动剂以及8-羟基二丙胺、丁螺环酮和（+）-氟西汀进行的相关性分析显示，它们在增强受罚反应方面的相对效力与其在体外对5-羟色胺1A受体的亲和力之间存在显著相关性（r = +0.95，p < 0.001）。得出结论，S 14671在鸽子冲突试验中是一种异常强效且有效的配体，其抗焦虑作用反映了5-羟色胺1A受体的激活。
