Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Laboratório de Farmacologia Aplicada e Toxicologia, Universidade de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2009 Jun;42(6):556-60. doi: 10.1590/s0100-879x2009000600013.
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.
内源性大麻素系统参与许多生理功能的控制，包括情绪状态的控制。在啮齿动物中，先前暴露于开阔场会增加高架十字迷宫中的焦虑样行为。增加内源性大麻素水平的药理学化合物的抗焦虑样作用已有充分记录。然而，这些作用在焦虑水平较高的动物中更为明显。几项研究描述了调节内源性大麻素水平的药物的特征倒 U 形剂量反应效应。然而，没有研究显示外源性大麻素（一种内源性大麻素）在焦虑动物模型中的不同剂量的作用。因此，在本研究中，我们确定了外源性大麻素在 C57BL/6 小鼠（N = 10/组）中的剂量反应效应，这些小鼠依次接受了开阔场和高架十字迷宫测试。大麻素用 0.9%生理盐水、乙醇、Emulphor（18:1:1）稀释，并腹腔注射（0.1 mL/10 g 体重）；对照动物接受相同体积的大麻素载体。大麻素 0.1 mg/kg（但不是 0.01 或 1 mg/kg）增加了（P < 0.05）开阔场中央区域的停留时间和距离，以及高架十字迷宫的开放臂探索。因此，外源性大麻素与增加内源性大麻素水平的药理学化合物一样，在焦虑动物模型中产生了特征性的倒 U 形剂量反应效应。此外，大麻素（0.1 mg/kg）在暴露于开阔场测试后在高架十字迷宫中诱导出抗焦虑样作用（P < 0.05）。
