Effects of melatonin on neophobic responses in different strains of mice

Anxiolytic properties of melatonin in rodents had usually been examined in behavioral tests based on stressful situations, i.e., in animal models of " state" anxiety. However, no study reports effects of melatonin on emotional ity of rodents submitted to situations devoid of stressful components as in the free-exploratory test, which gives to animals the opportunity to choos e freely between familiar and unfamiliar places. This procedure has been pr oposed as a method for measuring an endogenous form of anxiety called "trai t" anxiety. The present study first investigated the effects of melatonin o n neophobic responses of male C57BL/6, C3H/He, and BALB/c mice submitted to a free-exploratory test. Results demonstrated that melatonin had no effect in C57BL/6 mice that presented very low neophobic responses, whereas it wa s effective in reducing neophobia of BALB/c and C3H/He mice that presented, respectively, strong and intermediate avoidance responses towards unfamili arity. Indeed, mice of both latter strains treated with melatonin made fewe r attempts to enter into the unfamiliar compartment, exhibited a lower late ncy of the first entry into the unfamiliar places, and spent more time in t hem. Thus, melatonin appeared to be equally effective in reducing "trait" a nxiety in both BALB/c and C3H/He mice. Moreover, flumazenil was able to cou nteract, in a dose-dependent manner, the anxiolytic activity of melatonin i n BALB/c, suggesting involvement of central GABAergic system in the pharmac ological effects of melatonin. (C) 1999 Elsevier Science Inc.