ANTIDEPRESSANT-LIKE EFFECTS OF ALNESPIRONE (S-20499) IN THE LEARNED HELPLESSNESS TEST IN RATS

The effects of the new chroman derivative, alnespirone (S 20499). whic h is a selective 5-HT1A receptor agonist, were investigated in an anim al model of depression, the learned helplessness test. Rats previously submitted to a session of 60 inescapable electric foot shocks (learne d helpless controls) exhibited a deficit in escape performance in thre e subsequent shuttle-box sessions. Alnespirone was administered tu ice daily via the oral route (1.5, 5, 10, 20 mg kg(-1) day(-1)). It was s hown to protect against the elevation in escape failures caused by exp osure to the uncontrollable aversive situation at 5 and 10 mg hg(-1) d ay(-1) p.o. (13 +/- 2 and 10 +/- 3 escape failures, respectively. vs. 9 +/- 2 escape failures in control rat,). In addition, alnespirone had 3 tendency to elevate the number of intertrial crossings during the r esting periods, depending on the dose and day on which the avoidance t ask was performed (15 +/- 7 intertrial crossings at the dose of 5 mg k g(-1) day(-1), vs. 5 +/- 2 intertrial crossings for the helpless contr ol rats, on the second day). In comparison, imipramine (64 mg kg(-1) d ay(-1) p.o.) provided marked protection on all three days of the avoid ance task and tended to increase the number of intertrial crossings du ring the resting periods on the second and the third days. It is concl uded that alnespirone exerts antidepressant-like properties in the lea rned helplessness test in rats, in a manner similar to 8-OH-DPAT (8-hy droxy-2-(di-n-propylamino)tetralin), buspirone and ipsapirone. other 5 -HT1A receptor agonists. (C) 1998 Elsevier Science B.V.