Effects of olanzapine on anxiety-related behaviour in male and female rats assessed after 21-24 and 42-45 days of chronic treatment.

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.