Sensorimotor gating deficits are inheritable in an isolation-rearing paradigm in rats

Early life experience is a key etiological factor of neuropsychiatric dysfunctions and is associated with developmental origins. Impaired prepulse inhibition (PPI) following an acoustic startle response is acknowledged as a cardinal characteristic in socially deprived weanling rats, which has been employed to investigate the underlying mechanisms of sensorimotor gating abnormalities in certain mental disorders, including schizophrenia. Because impaired PPI is a postnatal malfunction, it is interesting to examine whether it can be passed to the next generation. Isolation-rearing (IR) rats had been socially deprived since weaning, which mated with social rearing rats. Next, the offspring of IR rats were reared in a normal social environment. Locomotion, PPI, monoamines, and genes in schizophrenia-relevant brain areas [medial prefrontal cortex (mPFC) and hippocampus] were later measured. To this end, we observed that the next generation of IR offspring rats appeared with impaired PPI in which the PPI deficit can be observed as early as three weeks after birth. The third generation also exhibited lower levels of dopamine and serotonin in the mPFC and hippocampus; however, higher levels of both monoamines were measured in the striatum. Finally, Slc1a2 was more highly expressed in the mPFC of the third generation male rats. The present study demonstrates a transgenerational inheritance of IR-induced character and may help to elucidate the underlying pathoetiology of schizophrenia.