THE EFFECTS OF THE 5-HT1A AGONIST FLESINOXAN, IN 3 PARADIGMS FOR ASSESSING ANTIDEPRESSANT POTENTIAL IN THE RAT

5-HT1A receptor agonists have been shown to be effective clinically in the treatment of depression and anxiety. Flesinoxan is an example whi ch is highly selective for the 5-HT1A receptor subtype. The objective of this study was to appraise the antidepressant potential of flesinox an (1 and 3 mg/kg s.c.) in three tests which are indicative of antidep ressant activity. These are (1) the forced swim test, following sub-ac ute administration, (2) 'open field' activity in the olfactory bulbect omised (OB) rat, following chronic administration, and (3) 8-OH-DPAT-i nduced hypothemia following chronic treatment. Both doses of flesinoxa n significantly reduced the immobility time in the sham and OB groups when compared to their respective controls. In the 'open field', there was a significant increase in the ambulation of the OB control group. The higher dose of flesinoxan significantly reduced this deficit. In addition both doses of flesinoxan significantly attenuated the 8-OH-DP AT induced hypothermic response. These effects of flesinoxan are quant itatively similar to those seen following the chronic administration o f antidepressants. These studies illustrate the potential antidepressa nt properties of flesinoxan, and hence further emphasise the role of t he 5-HT1A receptor in the pathogenesis of depression. (C) 1997 Elsevie r Science B.V.