Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, Smętna St. 12, 31-343, Kraków, Poland.
Neurotox Res. 2018 Aug;34(2):305-323. doi: 10.1007/s12640-018-9888-0. Epub 2018 Mar 13.
Social isolation (SI) during adolescence may induce schizophrenia-like behavior. In the present study, we investigated whether adolescent SI might affect the development of schizophrenia-like behavior in the MAM-E17 neurodevelopmental model of schizophrenia. Rats were socially isolated for 10 days during adolescence (postnatal days (P) 30-40), followed by resocialization until late adolescence (P45-P48) or early adulthood (P70-P75); behavioral and neurochemical studies were performed at these ages. The behavioral studies analyzed locomotor activity, social interaction, recognition memory, and sensorimotor gating; GAD65 and GAD67 protein levels were measured in the prefrontal cortex. The results showed that SI did not affect locomotor activity, but it prevented the social interaction deficits induced by MAM administration at both of the analyzed age points. However, SI induced a deficit in recognition memory in the MAM group during adolescence, which was not observed in the MAM-treated, socially housed rats at this age. In adulthood, impairments in recognition memory were detected in both MAM groups. In contrast, SI did not accelerate the appearance of sensorimotor gating deficits in MAM animals during adolescence, and sensorimotor gating impairments were observed in both MAM groups during adulthood. Adolescent SI rearing did not affect any examined behavioral responses in the VEH-treated groups. SI altered the levels of GAD65 and GAD67 proteins during adolescence in both groups; however, the decrease in the level of GAD65 protein was observed only in the adult MAM-SI group. Thus, SI rearing during a defined period of adolescence might have specific effects on the emergence of schizophrenia-like abnormalities in MAM-treated animals.
社交隔离（SI）在青春期可能会诱发类似精神分裂症的行为。在本研究中，我们研究了青春期 SI 是否会影响 MAM-E17 精神分裂症神经发育模型中类似精神分裂症行为的发展。在青春期（出生后第 30-40 天）期间，大鼠被社交隔离 10 天，然后进行再社会化，直到青春期后期（P45-P48）或成年早期（P70-P75）；在这些年龄进行行为和神经化学研究。行为研究分析了运动活动、社交互动、识别记忆和感觉运动门控；在前额叶皮层测量 GAD65 和 GAD67 蛋白水平。结果表明，SI 不影响运动活动，但可预防 MAM 给药引起的社交互动缺陷，在分析的两个年龄点均有观察到。然而，SI 在青春期 MAM 组中引起识别记忆缺陷，但在这个年龄的 MAM 治疗、社交饲养的大鼠中没有观察到。在成年期，在两个 MAM 组中均检测到识别记忆障碍。相反，在青春期，SI 没有加速 MAM 动物感觉运动门控缺陷的出现，并且在成年期，在两个 MAM 组中都观察到感觉运动门控受损。青春期 SI 饲养在 VEH 治疗组中对任何检查的行为反应均无影响。SI 在两组中均改变了 GAD65 和 GAD67 蛋白的水平；然而，只有在成年 MAM-SI 组中才观察到 GAD65 蛋白水平下降。因此，在特定的青春期时期进行 SI 饲养可能会对 MAM 治疗动物中类似精神分裂症异常的出现产生特定影响。
