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 would produce antidepressant-like behavioral effects in the rodent forced swim model. The tricyclic antidepressant, imipramine, as well as the 5-HT1A receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and gepirone, produced dose-related decreases in immobility in the forced swim test following subchronic treatment in rats. LY228729, when given over a three injection course, as with the other compounds, significantly reduced immobility at doses of 1 and 3 mg/kg. Subsequent analysis of locomotor activity revealed no increases in behavior, so that general changes in activity could not account for the reduction in immobility time in the forced swim. These results suggest that LY228729 may have clinical antidepressant efficacy.