Department of Pharmacology and Toxicology, National Institute for Pharmaceutical Research and Development, Abuja, Nigeria.
Prog Neuropsychopharmacol Biol Psychiatry. 2012 Aug 7;38(2):310-6. doi: 10.1016/j.pnpbp.2012.04.018. Epub 2012 Apr 26.
Schizophrenia is a chronic and highly complex psychiatric disorder characterised by cognitive dysfunctions, negative and positive symptoms. The major challenge in schizophrenia research is lack of suitable animal models that mimic the core behavioural aspects and symptoms of this devastating psychiatric disorder. In this study, we used classical and atypical antipsychotic drugs to examine the predictive validity of ketamine-enhanced immobility in forced swim test (FST) as a possible animal model for the negative symptoms of schizophrenia. We also evaluated the effects of a selective serotonin reuptake inhibitor (SSRI) on the ketamine-enhanced immobility in FST. Repeated administration of a subanaesthetic dose of ketamine (30 mg kg(-1), i.p., daily for 5 days) enhanced the duration of immobility in FST 24 h after the final injection. The effect, which persisted for at least 21 days after withdrawal of the drug, was neither observed by single treatment with ketamine (30 mg kg(-1) i.p.) nor repeated treatment with amphetamine (1 and 2 mg kg(-1) i.p., daily for 5 days). The enhancing effects of ketamine (30 mg kg(-1) day(-1) i.p.) on the duration of immobility in the FST were attenuated by clozapine (1, 5 and 10 mg kg(-1) i.p.), risperidone (0.25 and 0.5 mg kg(-1) i.p.) and paroxetine (1 and 5 mg kg(-1) i.p.). Haloperidol (0.25 and 0.50 mg kg(-1) day(-1) i.p.) failed to attenuate the ketamine-enhanced immobility in the FST. The repeated ketamine administration neither affects locomotor activity nor motor coordination in rats under the same treatment conditions with the FST, suggesting that the effects of ketamine on the duration of immobility in this study was neither due to motor dysfunction nor peripheral neuromuscular blockade. Our results suggest that repeated treatment with subanaesthetic doses of ketamine enhance the duration of immobility in FST, which might be a useful animal model for the negative symptoms (particularly the depressive features) of schizophrenia.
精神分裂症是一种慢性且高度复杂的精神障碍，其特征为认知功能障碍、阳性和阴性症状。精神分裂症研究的主要挑战是缺乏合适的动物模型来模拟这种破坏性精神障碍的核心行为和症状。在这项研究中，我们使用经典和非典型抗精神病药物来检查氯胺酮增强的强迫游泳试验（FST）中的不动性是否可预测为精神分裂症阴性症状的动物模型。我们还评估了选择性 5-羟色胺再摄取抑制剂（SSRI）对 FST 中氯胺酮增强的不动性的影响。重复给予亚麻醉剂量的氯胺酮（30mg/kg，腹腔注射，每天一次，共 5 天）可增强最后一次注射后 24 小时的 FST 不动时间。这种作用在停药后至少 21 天内持续存在，单次氯胺酮（30mg/kg，腹腔注射）治疗或重复安非他命（1 和 2mg/kg，腹腔注射，每天一次，共 5 天）治疗均未观察到。氯胺酮（30mg/kg/天，腹腔注射）对 FST 中不动时间的增强作用被氯氮平（1、5 和 10mg/kg，腹腔注射）、利培酮（0.25 和 0.5mg/kg，腹腔注射）和帕罗西汀（1 和 5mg/kg，腹腔注射）减弱。氟哌啶醇（0.25 和 0.50mg/kg/天，腹腔注射）未能减弱 FST 中氯胺酮增强的不动性。在相同的 FST 治疗条件下，重复给予氯胺酮既不影响大鼠的运动活动也不影响运动协调，这表明氯胺酮对本研究中不动时间的影响既不是由于运动功能障碍也不是由于外周神经肌肉阻滞所致。我们的结果表明，重复给予亚麻醉剂量的氯胺酮可增强 FST 中的不动时间，这可能是精神分裂症阴性症状（特别是抑郁特征）的有用动物模型。
