Department of Pharmacology, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria.
Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
Metab Brain Dis. 2017 Oct;32(5):1475-1489. doi: 10.1007/s11011-017-0031-3. Epub 2017 May 15.
Effects of sertraline, haloperidol or olanzapine administration on ketamine-induced behaviours in mice were examined. The aim was to ascertain the degree of reversal of such behaviours by sertraline, and compare its effectiveness to haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into main groups; 1 (open-field, radial-arm maze and elevated plus maze {EPM} tests), and 2 (social interaction test). Mice in each main group were assigned into six groups of ten (n = 10) each. Group 1 received intraperitoneal (i.p) injection of vehicle, while groups 2-6 received i.p ketamine at 15 mg/kg daily for 10 days. From day 11 to 24, mice in group 1 (vehicle) were given distilled water (i.p at 2 ml/kg and oral at 10 ml/kg), group 2 (ketamine control) received daily i.p ketamine and oral distilled water; while animals in groups 3-6 received daily i.p. ketamine and oral haloperidol (4 mg/kg), olanzapine (2 mg/kg), or one of two doses of sertraline (SERT) (2.5 or 5 mg/kg), respectively. Treatments were administered daily, and behaviours assessed on days 11 and 24. Results showed that repeated ketamine administration caused hyperlocomotion, increased self-grooming, memory loss and social withdrawal. Administration of sertraline (both doses), haloperidol, and olanzapine reversed ketamine-induced behavioural changes. However, in the EPM, sertraline and olanzapine were anxiolytic, while haloperidol was anxiogenic. Sertraline's effect on behaviours tested was comparable to olanzapine and better than haloperidol. In conclusion, this study shows that sertraline's ability to counteract ketamine-induced behavioural changes in mice is comparable to known antipsychotics.
研究了舍曲林、氟哌啶醇或奥氮平给药对氯胺酮诱导的小鼠行为的影响。目的是确定舍曲林对这些行为的逆转程度，并比较其与氟哌啶醇和奥氮平的效果。将 10 周龄的小鼠（N=120）平均分为主要的 2 组；1 组（旷场实验、放射臂迷宫和高架十字迷宫实验）和 2 组（社交互动实验）。每组 10 只小鼠（n=10）分为 6 个小组。第 1 组接受腹腔注射（i.p）载体，而第 2-6 组每天接受 15mg/kg 的 i.p 氯胺酮，共 10 天。从第 11 天到第 24 天，第 1 组（载体）的小鼠接受腹腔内（i.p）注射蒸馏水（2ml/kg，口服 10ml/kg），第 2 组（氯胺酮对照组）接受每日 i.p 氯胺酮和口服蒸馏水；而第 3-6 组动物接受每日 i.p.氯胺酮和口服氟哌啶醇（4mg/kg）、奥氮平（2mg/kg）或两种剂量的舍曲林（SERT）（2.5 或 5mg/kg）。治疗每天进行，在第 11 天和第 24 天评估行为。结果表明，反复氯胺酮给药导致过度活跃、增加自我梳理、记忆丧失和社会回避。舍曲林（两种剂量）、氟哌啶醇和奥氮平给药逆转了氯胺酮诱导的行为变化。然而，在高架十字迷宫实验中，舍曲林和奥氮平具有抗焦虑作用，而氟哌啶醇具有焦虑作用。舍曲林对所测试行为的作用与奥氮平相当，优于氟哌啶醇。总之，这项研究表明，舍曲林在对抗小鼠氯胺酮诱导的行为变化方面的能力与已知的抗精神病药物相当。
