EFFECTS OF MELATONIN RECEPTOR LIGANDS ON SWIM TEST IMMOBILITY

THE Flinders Sensitive Line (FSL) rats have been proposed as a genetic animal model of depression because their innately high immobility in the forced swim test is counteracted by antidepressants. This model wa s used to test the acute and chronic effects of two novel compounds wh ich have either an agonist or antagonist-like effect at melatonin rece ptors. In the acute study FSL and control Flinders Resistant Line (FRL ) rats were unaffected by either the agonist S 20304 (1 or 20 mg/kg) o r the antagonist S 20928 (1 or 10 mg/kg) given 1 h prior to a single 5 min swim test. In the chronic study a reduction in immobility in the FSL rats at the highest dose of the agonist was the only significant d rug effect. These findings suggest that the melatonin receptor agonist S 20304 may have antidepressant potential.