The effects of an early stressful life event on sensorimotor gating in adult rats

Abstract

There is increasing evidence that patients suffering from schizophrenia have disturbances in the brain and other parts of the body indicative of a disturbed development. These findings have led to the so-called neurodevelopmental hypotheses of schizophrenia, which state that schizophrenia (or a predisposition for this disease) results from perinatal disturbances which affect the normal development of the central nervous system. In order to study such a possible relationship we have used early short-lasting (24 h) maternal deprivation, and studied the influence of this life event on prepulse inhibition of the acoustic startle at adult age in rats, since it has been shown that schizophrenic patients show a disruption of prepulse inhibition. The results show that early maternal deprivation significantly reduced prepulse inhibition when the animals were tested at postnatal day (pnd) 69 (birth being pnd 0). The effects were qualitatively similar when deprivation took place on pnd 3, 6 or 9, although at the later days the effects were stronger. There was little influence on baseline startle response (except for a small reduction seen after deprivation on pnd 6). In separate experiments it was shown that the effect of maternal deprivation on prepulse inhibition was not seen before puberty and was similar for male and female offspring. Moreover, the effects could be reversed by treatment with the classical antipsychotic, haloperidol, or the putative atypical antipsychotic, quetiapine (both given 15 min before the prepulse inhibition experiment). In summary, the results show that an early stressful life event can have a delayed influence on prepulse inhibition in rats, qualitatively similar to the disturbances seen in schizophrenic patients. These data suggest that maternal deprivation (i.e., a 24 h separation of rat pups from their mother early in life) may represent an interesting animal model for investigating the influence of early life events on the information processing and general functioning of an individual at adult age.