School of Psychology Speech and Hearing, University of Canterbury, Christchurch, New Zealand.
Behav Pharmacol. 2021 Apr 1;32(2&3):194-211. doi: 10.1097/FBP.0000000000000612.
Olanzapine can decrease anxiety and impair memory, but there is limited information about length of treatment or sex differences in its effectiveness. Therefore, effects of 21-24 and 41-45 days of treatment and sex differences on anxiety-related behaviour and spatial memory were assessed in PVG/c (PVG/c is the internationally recognised way of referring to this rat strain) male and female rats. From 70 days after birth (PND70), all rats received no drug or 6, 11 or 15 mg/kg/day olanzapine via drinking water. From PND91, they were given four daily tests in an open field, light-dark box, zero maze and Y maze, and then again 21 days later from PND112. At PND91-94, all olanzapine doses decreased open-field ambulation and walking, and 6 and 15 mg/kg/day decreased rearing, increased immobility while 15 mg/kg/day decreased shuttles in the light/dark box (all suggesting higher anxiety). At PND112-115, 11 mg/kg/day increased open-field ambulation, walking, rearing, centre occupancy and light/dark-box shuttles and light-side entries while decreasing open-field immobility and corner occupancy (all suggesting lower anxiety). There were also several results in the open field and light/dark box suggesting olanzapine decreased anxiety for males but increased it for females. A significant olanzapine-related preference for the novel Y-maze arm either improved spatial memory, or decreased anxiety. Olanzapine thus appeared anxiogenic after 21 days' treatment, becoming anxiolytic after 42 days. This could depend on the sex of the rats (females more responsive to lower doses), and the dose (11 mg/kg/day being most effective). Therefore, while olanzapine was generally anxiolytic, it also had some treatment length- and sex-related anxiogenic effects.
奥氮平可降低焦虑并损害记忆，但关于其治疗时间长短或疗效的性别差异的信息有限。因此，评估了 21-24 天和 41-45 天的治疗时间以及性别差异对 PVG/c（PVG/c 是指这种大鼠品系的国际公认方式）雄性和雌性大鼠的焦虑相关行为和空间记忆的影响。从出生后 70 天（PND70）开始，所有大鼠均通过饮用水接受无药物或 6、11 或 15mg/kg/天的奥氮平治疗。从 PND91 开始，它们在开阔场、明暗箱、零迷宫和 Y 迷宫中每天进行 4 次测试，然后在 PND112 后再进行 21 天测试。在 PND91-94 期间，所有奥氮平剂量均降低了开阔场的运动和行走，6 和 15mg/kg/天降低了直立，增加了不动性，而 15mg/kg/天降低了明暗箱中的穿梭次数（所有这些都表明焦虑程度更高）。在 PND112-115 期间，11mg/kg/天增加了开阔场的运动、行走、直立、中心占有率和明暗箱的穿梭和进入亮侧的次数，同时减少了开阔场的不动性和角落占有率（所有这些都表明焦虑程度更低）。在开阔场和明暗箱中也有一些结果表明，奥氮平降低了雄性的焦虑，而增加了雌性的焦虑。奥氮平对新奇的 Y 型迷宫臂的明显偏好要么改善了空间记忆，要么降低了焦虑。奥氮平在 21 天治疗后似乎具有焦虑作用，在 42 天后成为抗焦虑药。这可能取决于大鼠的性别（雌性对较低剂量的反应更敏感）和剂量（11mg/kg/天最有效）。因此，虽然奥氮平通常具有抗焦虑作用，但它也具有一些与治疗时间长短和性别相关的焦虑作用。
