Alterations in Nitric Oxide Production After Post-Weaning Social Isolation

Early-life stressful stimuli, such as social isolation, alter brain neurochemistry and lead to negative behavioral outcomes in adulthood. Isolated animals are deprived of social interactions, which results in impaired brain development. Post-weaning isolation rearing deregulates various brain processes and may affect nitric oxide (NO) signaling. The aim of our study was to determine time-dependent impact of social isolation on behavioral and biochemical parameters in Wistar Kyoto rats. At the age of 21 days, male rats were randomly assigned into four groups reared in isolation or socially for 10 or 29 weeks. At the end of the rearing, open-field and prepulse inhibition (PPI) tests were carried out. Furthermore, in several brain areas we assessed NO synthase (NOS) activity, protein expression of nNOS and iNOS isoforms and the concentration of conjugated dienes (CD), a marker of lipid peroxidation. The number of entries into the central zone of the open field test decreased significantly only after 29 weeks of isolation. Isolated rats (IR) rats exhibited impaired habituation of the acoustic startle response after prolonged social isolation. While cerebellar NOS activity and nNOS protein expression decreased significantly in IR rats after 29 weeks of isolation, the expression of nNOS and iNOS was increased in the hippocampus. 10-week and 29-week social isolation led to increased CD concentration in the brain. Our results suggest that the duration of social isolation plays an important role in the development of behavioral and biochemical changes in the brain. The decreased NO bioavailability may result from lipid peroxidation, oxidative stress, and inflammatory responses.