Volume 31 Issue 4 - March 3, 2017 PDF
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Social isolation-induced increased NMDA receptors in ventral hippocampus primes mice for aggressive behaviors
C.H. Chang, Y.H. Hsiao, Y.W. Chen, Y.J. Yu and Po-Wu Gean*
Department of Pharmacology, National Cheng-Kung University
 
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Family and social support is a critical factor for physical and psychological health for human being belonged to social animal. Prolong social isolation have long-term effects on the susceptibility to subsequent stress exposure. We used the animal model of post-weaning social isolation to research the behavioral responses to acute stress in adult mice. Rodent pups were separated and singly housed in the individual cages on postnatal day 21~28 and were given free access to water and food. The social isolation-reared (SI) mice only had visual, auditory and olfactory contact with other conspecifics without any form of physical interaction with each other.

During adulthood, SI mice exhibited a higher spontaneous locomotor activity. Schizophrenic patients have the deficient prepulse inhibition (PPI) of acoustic startle reflex, which is used to assess the subject’s ability to gate or filter environmental information for the integration of cognitive and sensory information. We found post-weaning social isolation also impaired the PPI of mice, indicating abnormalities of sensorimotor gating. SI mice also exhibited a higher level of despaired behavior in the forced swimming test, suggesting the depression-like phenotype. In the social interaction test, SI mice exhibited more offensive behaviors but not attack number compared with group housing (GH) mice. However, acute stress significantly exacerbated attack counts of SI mice to the intruder mice and induced higher levels of anxiety-like behavior in the open field test. These results suggested that post-weaning social isolation induced susceptibility to acute stress and exaggerated attack behavior in mice.

Moreover, SI mice exhibited an increased level of NR2B subunit of NMDA receptors in the hippocampus. The NMDA receptor inhibitor or a specific NR2B inhibitor was infused into hippocampus of SI mice reversed acute stress-induced exaggeration of aggressive behavior. In addition, the specific knockdown of NR2B expression in the hippocampus by shRNA transfection technique significantly reduced the stress-induced attack level of SI mice. These results suggested the isolation-induced increased levels of NMDA receptors in the hippocampus may mediate the stress-induced aggression.
Figure 1: The socially isolated (SI) mice exaggerated attack behavior after acute stress. GH: group housing mice, SI: socially isolated mice; white bar: no stress, black bar: acute stress.

Figure 2: (A) SI mice exhibited an increased level of NR2B subunit of NMDA receptors in the hippocampus. (B) The specific knockdown of NR2B expression in the hippocampus by shRNA transfection technique significantly reduced the stress-induced attack level of SI mice. GH: group housing mice, SI: socially isolated mice; white bar: scramble control, black bar: NR2B shRNA.
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