ANTIDEPRESSANT-LIKE EFFECT OF LY228729 AS MEASURED IN THE RODENT FORCED SWIM PARADIGM

The novel 5-HT1A receptor agonist, LY228729, was tested to see if it w ould produce antidepressant-like behavioral effects in the rodent forc ed swim model. The tricyclic antidepressant, imipramine, as well as th e 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8- OH-DPAT) and gepirone, produced dose-related decreases in immobility i n the forced swim test following subchronic treatment in rats. LY22872 9, when given over a three injection course, as with the other compoun ds, significantly reduced immobility at doses of 1 and 3 mg/kg. Subseq uent analysis of locomotor activity revealed no increases in behavior, so that general changes in activity could not account for the reducti on in immobility time in the forced swim. These results suggest that L Y228729 may have clinical antidepressant efficacy.