Antidepressant-like effects of alnespirone (S 20499) in the learned helplessness test in rats

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.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Anxiety Agents / therapeutic use*
  • Depression / drug therapy*
  • Helplessness, Learned*
  • Male
  • Rats
  • Rats, Wistar
  • Serotonin Receptor Agonists / therapeutic use*
  • Spiro Compounds / therapeutic use*


  • Anti-Anxiety Agents
  • Serotonin Receptor Agonists
  • Spiro Compounds
  • alnespirone