Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, UMC Utrecht, Utrecht, The Netherlands.
Neuropsychopharmacology. 2013 Jul;38(8):1485-94. doi: 10.1038/npp.2013.47. Epub 2013 Feb 12.
Social experiences during youth are thought to be critical for proper social and cognitive development. Conversely, social insults during development can cause long-lasting behavioral impairments and increase the vulnerability for psychopathology later in life. To investigate the importance of social experience during the juvenile and early adolescent stage for the development of cognitive control capacities, rats were socially isolated from postnatal day 21 to 42 followed by re-socialization until they reached adulthood. Subsequently, two behavioral dimensions of impulsivity (impulsive action in the five-choice serial reaction time task (5-CSRTT) and impulsive choice in the delayed reward task) and decision making (in the rat gambling task) were assessed. In a separate group of animals, long-lasting cellular and synaptic changes in adult medial prefrontal cortex (PFC) pyramidal neurons were determined following social isolation. Juvenile and early adolescent social isolation resulted in impairments in impulsive action and decision making under novel or challenging circumstances. Moreover, socially isolated rats had a reduced response to enhancement of dopaminergic neurotransmission (using amphetamine or GBR12909) in the 5-CSRTT under challenging conditions. Impulsive choice was not affected by social isolation. These behavioral deficits were accompanied by a loss of sensitivity to dopamine of pyramidal neurons in the medial PFC. Our data show long-lasting deleterious effects of early social isolation on cognitive control and its neural substrates. Alterations in prefrontal cognitive control mechanisms may contribute to the enhanced risk for psychiatric disorders induced by aberrations in the early social environment.
青少年时期的社会经历被认为对正常的社会和认知发展至关重要。相反,发育过程中的社会侮辱会导致持久的行为障碍,并增加日后患精神病理学的脆弱性。为了研究青少年和早期青少年阶段的社会经验对认知控制能力发展的重要性,研究人员将大鼠从出生后第 21 天至第 42 天进行社交隔离,然后进行再社会化,直到它们成年。随后,评估了冲动性的两个行为维度(在五选择连续反应时间任务(5-CSRTT)中的冲动行为和延迟奖励任务中的冲动选择)和决策(在大鼠赌博任务中)。在另一组动物中,确定了社交隔离后成年内侧前额叶皮层(PFC)锥体神经元的长期细胞和突触变化。青少年和早期青少年的社交隔离导致在新的或具有挑战性的情况下冲动行为和决策能力受损。此外,在具有挑战性的条件下,社交隔离的大鼠在 5-CSRTT 中对多巴胺能神经传递的增强(使用安非他命或 GBR12909)的反应减少。冲动选择不受社交隔离的影响。这些行为缺陷伴随着内侧 PFC 锥体神经元对多巴胺敏感性的丧失。我们的数据显示,早期社交隔离对认知控制及其神经基质有持久的有害影响。前额叶认知控制机制的改变可能导致早期社会环境异常引起的精神障碍风险增加。