The
endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze.
Anxiolytic-like effects of pharmacological compounds that increase
endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the
endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous
anandamide, an
endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous
anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze.
Anandamide was diluted in
0.9% saline,
ethyl alcohol,
Emulphor (18:1:1) and administered ip (0.1 mL/10 g
body weight); control animals received the same volume of
anandamide vehicle.
Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous
anandamide, like pharmacological compounds that increase
endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore,
anandamide (0.1 mg/kg) induced an
anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.