ELSEVIER Schizophrenia Research 3(I ( 1998) 251 26(I SCHIZOPHRENIA RESEARCH The effects of an early stressful life event on sensorimotor gating in adult rats Bart A. Ellenbroek *, Peter T.J.M. van den Kroonenberg, Alexander R. Cools lnir~'rsit r ~l:V!/nwgen. Departnwnl (?/P.v.rcl~oneurol~/~arnlacolo£:r. P.O. Box 9101. 6500 HB ..Vi/n~egen. The Nettwr/am/x Received 22 July 1997: accepted 18 November 1997 Abstract Thc,e 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 lk)r this disease) resuhs 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 (pndt 69 t birth being pnd Iit. The effects were qualitatively similar when deprivation took place on pnd 3.6 or 9, ahhough at the later days the efl'ects were stronger. There was little influence on baseline startle response (except for a small reduction seen after depriwttion on pnd 6). In separate experiments it was shown that the effect of maternal deprivation on prepulse inhibition was not seen bel\~re puberty and was similar t\~r male and female offspring. Moreover, the effects could be reversed by' treatlnent with the chtssical antipsychotic, haloperidol, or the putative atypical antipsychotic, quetiapine (both given 15 mm bel\~re 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 m schizoph,enic 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 l\~r investigating the influence of early life events on the inl\~rmation processing and general functioning of an individual at aduh age. ,c: 1998 Elsevier Science B.V. Kevu'+~rd.v Eal+ly stressful life event: Sensorimotor gating: Neurodevelopmental hypotheses: Schizophrenia I. Introduction It has long been realised that development in mammals is profoundly influenced by experiences occurring during infancy ( Hofer, 1970: Hinde and * Corresponding author. Tel: + 31 - 24 - 3616479: Vax: t 31 - 24 - 3540044: e-mail: A.ellenbroek(apnf.kun.nl 0920-9t;64 98 $19.110c 1998 ElsexierScience B.V. All rights reserved. PII SI)t)21)-c)964(97 )00149-7 Spencer-Booth, 1971 ). Most of the more system- atic studies of the last years have concentrated oll the neuroendocrine response to stressors, after an early stressful life event like maternal deprivation. It has been shown that rats, maternally deprived for 24 h at postnatal day 3. show a much stronger and enduring increase ill plasma glucocorticoid levels than control rats at adull age (Rots el al.,