Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany.
Int J Neuropsychopharmacol. 2011 Feb;14(1):43-51. doi: 10.1017/S1461145710000842. Epub 2010 Aug 3.
Chronic pubertal cannabinoid treatment in rats has been suggested for modelling aspects of schizophrenia since it results in long-lasting behavioural alterations reflecting certain characteristics of schizophrenia symptomatology. Lasting deficits in sensorimotor gating, impaired short-term mnemonic processing, reduced motivation as well as inappropriate and deficient social behaviour have been reported after chronic cannabinod treatment during pubertal development. In addition, sensorimotor gating deficits were able to be restored by acute injections of the typical antipsychotic haloperidol. The aim of this study was to examine possible acute as well as lasting beneficial effects of the atypical antipsychotic drug quetiapine in adult animals undergoing chronic treatment of the synthetic cannabinoid receptor agonist WIN 55,212-2 (WIN) (1.2 mg/kg) during puberty. Therefore, animals were tested repeatedly for their performance in social interaction and social recognition after acute and chronic quetiapine treatment. Chronic pubertal WIN treatment induced persistent deficits in social recognition and impaired social interaction. Acute quetiapine treatment was able to completely restore those deficits in social behaviour and social memory. Social recognition memory was affected again 1 wk after cessation of chronic quetapine treatment; however, in social interaction persistent improvements could be detected. In conclusion, the results indicate that the atypical antipsychotic drug quetiapine is able to acutely restore deficits in social behaviour induced by developmental cannabinoid exposure and even exert some persistent beneficial effects. Furthermore, the present data give further support and validity for the suitability of chronic pubertal cannabinoid administration as an animal model for aspects of schizophrenia.
慢性青春期大麻素处理已被建议用于模拟精神分裂症的某些方面,因为它会导致持久的行为改变,反映出精神分裂症症状学的某些特征。在青春期发育期间进行慢性大麻素处理后,已经报道了持续的感觉运动门控缺陷、短期记忆处理受损、动机降低以及不适当和不足的社会行为。此外,急性注射典型抗精神病药氟哌啶醇可恢复感觉运动门控缺陷。本研究的目的是检查在成年动物中进行慢性治疗合成大麻素受体激动剂 WIN 55,212-2 (WIN) (1.2 mg/kg) 期间,非典型抗精神病药喹硫平是否具有急性和持久的有益作用。因此,在急性和慢性喹硫平治疗后,动物被反复测试其在社交互动和社交识别方面的表现。慢性青春期 WIN 处理导致持续的社会识别缺陷和社交互动受损。急性喹硫平治疗能够完全恢复这些社会行为和社会记忆缺陷。慢性喹硫平治疗停止 1 周后,社会识别记忆再次受到影响;然而,在社交互动中仍能检测到持续的改善。总之,结果表明,非典型抗精神病药喹硫平能够急性恢复发育性大麻素暴露引起的社会行为缺陷,甚至发挥一些持久的有益作用。此外,本数据进一步支持和验证了慢性青春期大麻素给药作为精神分裂症某些方面的动物模型的适用性。