Mac Sweeney C P, Lesourd M, Gandon J M
Biotrial, Preclinical Studies Department, Rennes, France.
Eur J Pharmacol. 1998 Mar 19;345(2):133-7. doi: 10.1016/s0014-2999(97)01611-7.
The effects of the new chroman derivative, alnespirone (S 20499), which is a selective 5-HT1A receptor agonist, were investigated in an animal model of depression, the learned helplessness test. Rats previously submitted to a session of 60 inescapable electric foot shocks (learned helpless controls) exhibited a deficit in escape performance in three subsequent shuttle-box sessions. Alnespirone was administered twice daily via the oral route (2.5, 5, 10, 20 mg kg(-1) day(-1)). It was shown to protect against the elevation in escape failures caused by exposure to the uncontrollable aversive situation at 5 and 10 mg kg(-1) day(-1) p.o. (13+/-2 and 10+/-3 escape failures, respectively, vs. 9+/-2 escape failures in control rats). In addition, alnespirone had a tendency to elevate the number of intertrial crossings during the resting periods, depending on the dose and day on which the avoidance task was performed (15+/-2 intertrial crossings at the dose of 5 mg kg(-1) day(-1), vs. 5+/-2 intertrial crossings for the helpless control rats, on the second day). In comparison, imipramine (64 mg kg(-1) day(-1) p.o.) provided marked protection on all three days of the avoidance task and tended to increase the number of intertrial crossings during the resting periods on the second and the third days. It is concluded that alnespirone exerts antidepressant-like properties in the learned helplessness test in rats, in a manner similar to 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), buspirone and ipsapirone, other 5-HT1A receptor agonists.
新型色满衍生物阿奈螺酮（S 20499）是一种选择性5-羟色胺1A（5-HT1A）受体激动剂，本研究在抑郁动物模型——习得性无助试验中对其效果进行了调查。先前接受过60次不可逃避的足部电击（习得性无助对照组）的大鼠，在随后的三个穿梭箱试验环节中表现出逃避能力缺陷。阿奈螺酮通过口服途径每日给药两次（2.5、5、10、20毫克/千克/天）。结果显示，在口服剂量为5和10毫克/千克/天时，阿奈螺酮可防止暴露于不可控厌恶情境所导致的逃避失败次数增加（分别为13±2次和10±3次逃避失败，而对照大鼠为9±2次逃避失败）。此外，根据给药剂量以及进行回避任务的天数，阿奈螺酮有增加休息期穿梭次数的趋势（在剂量为5毫克/千克/天时为15±2次穿梭，而习得性无助对照大鼠在第二天为5±2次穿梭）。相比之下，丙咪嗪（口服剂量为64毫克/千克/天）在回避任务的所有三天中均提供了显著的保护作用，并且在第二天和第三天休息期有增加穿梭次数的趋势。得出的结论是，阿奈螺酮在大鼠习得性无助试验中具有类似抗抑郁的特性，其作用方式与其他5-HT1A受体激动剂8-OH-DPAT（8-羟基-2-（二正丙基氨基）四氢萘）、丁螺环酮和伊沙匹隆相似。
