The long-term effects of maternal deprivation depend on the genetic background

Abstract

The neurodevelopmental hypothesis of schizophrenia has led to a series of new animal models in which the long term consequences of early manipulations are investigated. We have recently shown that a single 24-hr period of maternal deprivation (at postnatal day (pnd) 9) increases apomorphine susceptibility and decreases prepulse inhibition in Wistar rats, viz. phenomena also seen in schizophrenic patients. In the present paper, we investigated whether the effects of maternal deprivation were dependent on a specific genetic background, by using different rat strains (Fischer 344 and Lewis) that differ in the Hypothalamus-Pituitary-Adrenal axis and in dopaminergic sensitivity. The data show that in Wistar rats, basal startle amplitude was not affected by maternal deprivation, but prepulse inhibition was reduced, and apomorphine susceptibility enhanced. In Fischer 344 rats on the other hand, neither basal startle amplitude, nor prepulse inhibition were affected, but apomorphine susceptibility was reduced. In Lewis rats, maternal deprivation significantly reduced basal startle amplitude, but did not affect prepulse inhibition or apomorphine susceptibility. The differential response to maternal deprivation can best be explained by differences in baseline dopamine sensitivity between the rat strains. Since a reduced prepulse inhibition and an enhanced susceptibility to apomorphine is also seen in schizophrenic patients, the data indicate that maternally deprived Wistar rats may represent an interesting developmental model for (aspects of) schizophrenia.