Antagonistic effects of S 22153, a new mt1 and MT2 receptor ligand, on the neophobia-reducing properties of melatonin in BALB/c mice.

When exposed to a free-exploratory situation, BALB/c mice are well known to exhibit strong avoidance responses toward unfamiliar places (neophobia). Because melatonin was found to significantly reduce neophobia in BALB/c mice, it seemed interesting to examine potential antagonistic effects of S 22153, a new melatonin mt1 and MT2 receptor ligand, on the neophobia-reducing properties of melatonin in BALB/c mice confronted with the free-exploratory paradigm. S 22153 was able to block, in a dose-dependent manner, the anxiolytic-like properties of melatonin when it was administered 5 min before melatonin. The antagonistic effects of S 22153 persisted when the drug was administered 2 or 4 h before melatonin, and were almost abolished when it was administered 6 h before melatonin. These results suggest that the anxiolytic-like effects of melatonin on the neophobic responses in BALB/c mice are mediated by mt1 and/or MT2 receptors.