Zugno A I, de Miranda I M, Budni J, Volpato A M, Luca R D, Deroza P F, de Oliveira M B, Heylmann A S, da Rosa Silveira F, Wessler P, Antunes Mastella G, Cipriano A L, Quevedo J
Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Laboratório de Neurociências, Instituto Nacional de Ciência e Tecnologia Translacional em Medicina (INCT-TM), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Neuroscience. 2013 Sep 17;248:252-60. doi: 10.1016/j.neuroscience.2013.05.059. Epub 2013 Jun 14.
Maternal deprivation has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. A growing number of studies demonstrated the importance of childhood experiences in the development of psychosis and schizophrenia in adulthood. Therefore, the present study investigated different behavior responses in rats following maternal deprivation and/or ketamine treatment in adulthood. Male rats were subjected to maternal deprivation for 180 min from postnatal day-01 to postnatal day-10. We evaluated locomotor activity, avoidance task and social interaction of adult male rats deprived or not deprived that were administered with saline or acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg, i.p.). Our results show that only ketamine (25 mg/kg, i.p.) treatment in the adult rats lead to hyperlocomotion but not ketamine (5 and 15 mg/kg) and maternal deprivation alone. However, maternally deprived rats treated with ketamine (5 mg/kg) induced hyperlocomotion. Additionally, ketamine (25 mg/kg) and maternal deprivation alone induced cognitive deficit in the avoidance task. Rats deprived of and treated with ketamine (5, 15 and 25 mg/kg) also lead to memory deficit. Moreover, ketamine (25 mg/kg) and maternal deprivation alone increased latency to start social behavior. However, ketamine (5 mg/kg) and maternal deprivation lead to an increase of latency to start social behavior. Biochemistry data showed that all doses of ketamine and ketamine plus maternal deprivation increased the acetylcholinesterase (AChE) activity in the prefrontal cortex, hippocampus and striatum. The major doses of ketamine associated with maternal deprivation induced a major increase of AChE activity. Together, our results suggest that animals subjected to maternal deprivation had an increased risk for schizophrenia-like behavior and cholinergic alteration.
母婴分离与生理和发育变化有关，这些变化可能与儿童期和成人期神经精神疾病风险增加有关。越来越多的研究表明童年经历在成年期精神病和精神分裂症发展中的重要性。因此，本研究调查了成年大鼠在母婴分离和/或氯胺酮治疗后的不同行为反应。雄性大鼠在出生后第1天至第10天接受180分钟的母婴分离。我们评估了给予生理盐水或急性亚麻醉剂量氯胺酮（5、15和25mg/kg，腹腔注射）的成年雄性大鼠在运动活动、回避任务和社交互动方面的情况，这些大鼠分为经历过母婴分离和未经历过母婴分离两组。我们的结果表明，仅成年大鼠腹腔注射氯胺酮（25mg/kg）会导致运动亢进，但氯胺酮（5和15mg/kg）以及单独的母婴分离不会导致运动亢进。然而，接受氯胺酮（5mg/kg）治疗的母婴分离大鼠会出现运动亢进。此外，单独的氯胺酮（25mg/kg）和母婴分离会导致回避任务中的认知缺陷。接受氯胺酮（5、15和25mg/kg）治疗且经历过母婴分离的大鼠也会导致记忆缺陷。而且，单独的氯胺酮（25mg/kg）和母婴分离会增加开始社交行为的潜伏期。然而，氯胺酮（5mg/kg）和母婴分离会导致开始社交行为的潜伏期增加。生化数据表明，所有剂量的氯胺酮以及氯胺酮加母婴分离都会增加前额叶皮质、海马体和纹状体中的乙酰胆碱酯酶（AChE）活性。与母婴分离相关的氯胺酮主要剂量会导致AChE活性大幅增加。总之，我们的结果表明，经历过母婴分离的动物出现精神分裂症样行为和胆碱能改变的风险增加。
