The Effects of Early Maternal Deprivation on Auditory Information Processing in Adult Wistar Rats Bart A. Ellenbroek, Natasja M.W.J. de Bruin, Peter T.J.M. van Den Kroonenburg, Egidius L.J.M. van Luijtelaar, and Alexander R. Cools Background: There is now ample evidence that schizophrenia is due to an interaction between genetic and (early) environmental factors which disturbs normal development of the central nervous system and ultimately leads to the development of clinical symptoms. Recently, we showed that a single 24-hour period of maternal deprivation of rat pups at postnatal day 9 leads to a disturbance in prepulse inhibition, similar to what is seen in schizophrenia. The present set of experiments was designed to further characterize the information processing deficits of maternally deprived Wistar rats. Methods: Wistar rats were deprived from their mother for 24 hours on postnatal day 9. At adult age, rats were tested in the acoustic startle paradigm for prepulse inhibition and startle habituation. Rats were also tested in the evoked potentials paradigm for auditory sensory gating. Results: The results show that maternal deprivation led to a reduction in acoustic startle habituation and auditory sensory gating in adult rats. Moreover, maternal deprivation disrupted prepulse inhibition but only when the prepulses were given shortly (50 –100 milliseconds) before the startle stimulus. At longer intervals (250 –1000 milliseconds), no effect was seen. Conclusions: The implications for the model and the development of disturbances in information processes are discussed. Key Words: Animal model, auditory sensory gating, acoustic startle habituation, prepulse inhibition, schizophrenia, neuro- development I n normal daily life, individuals are exposed to a large number of different external (and internal) stimuli. To adequately cope with these demands, a number of information process- ing mechanisms have emerged. These mechanisms have been conceptualized as filtering processes by a number of authors (Carr and Wale 1986; Treisman and Gelade 1980; Broadbent 1971). In general, these authors differentiate between two types of filters: 1) A fast (parallel) quantitative filter, generally referred to as sensory gating, and 2) a slower (serial) qualitative filtering mechanism, generally referred to as selective attention (Carr and Wale 1986). Given its fundamental nature, it is not surprising that deficits in information processing can lead to strong disturbances in cognition and behavior. One of the most prominent examples of diseases in which information processing deficits occur is schizo- phrenia (Braff 1993; Carr and Wale 1986). In this severe psychi- atric disease, disturbances in both sensory gating and selective attention have been described. Patients with schizophrenia have less sensorimotor gating, as measured with the prepulse inhibi- tion paradigm (Braff et al 1978; Kumari et al 2000; Mackeprang et al 2002; Weike et al 2000), and a reduction in the speed of habituation of the acoustic startle response (Braff et al 1992). In addition, these patients also have shown less sensory gating, as measured with the P 50 evoked potential paradigm (Adler et al 1982; Judd et al 1992; Freedman et al 1987). This latter paradigm is also referred to as auditory sensory gating. These paradigms have the clear advantage that they can be studied in humans and animals with virtually identical tech- niques, thus offering the opportunity to study the neuronal basis, as well as the development of these information pro- cessing deficits (Ellenbroek and Cools 1995a, 2000a; Geyer and Markou 1995). The plethora of clinical evidence that schizophrenia has a neurodevelopmental component (Weinberger 1996; Pilowsky et al 1993) has led to the development of novel animal models for schizophrenia, focusing specifically on the long-term conse- quences of early environmental manipulations. Thus, it has been shown that early postnatal lesions of the hippocampus (Lipska et al 1995; Le Pen and Moreau 2002) or of the dopaminergic system (Schwarzkopf et al 1992) and isolation rearing (Geyer et al 1993; Varty and Higgins 1995) disrupt prepulse inhibition. Much less is known with respect to the effects of such early manipulations on sensory gating and habituation. Isolation rearing was found to reduce sensory gating (Stevens et al 1997) but to leave startle habituation intact (Varty and Geyer 1998). Likewise, early lesions of the dopaminergic system did not affect sensory gating in adult rats (Stevens et al 1996). Recently, we showed that a single 24-hour period of maternal deprivation (MD) early in life significantly reduced prepulse inhibition in postpubertal rats, an effect which could be tempo- rarily reversed by antipsychotic treatment (Ellenbroek and Cools 2000b; Husum et al 2002; Ellenbroek et al 1998). We have subsequently shown that these maternally deprived animals also share other features with schizophrenic patients, such as an enhanced sensitivity to dopaminergic drugs and stress, as well as a reduction in latent inhibition (Ellenbroek and Cools 1995b, 2002a). Moreover, maternal deprivation seems to predominantly affect the hippocampal formation (Husum et al 2002; Roceri et al 2002), a neuronal structure often implicated in the neuropathol- ogy of schizophrenia (Weinberger 1999; Harrison 1999). All these data together have led to the hypothesis that the maternally deprived rat might represent an interesting animal model for specific aspects of schizophrenia. The aim of the present study was to further characterize the behavioral consequences of early maternal deprivation. More specifically, we have investigated the effects on sensory and sensorimotor gating and startle habituation. From the Departments of Psychoneuropharmacology (BAE, NMWJdB, PTJMvDK, ARC) and Comparative and Physiological Psychology (NMWJdB, ELJMvL), Nijmegen Institute for Cognition and Information, Nijmegen, The Netherlands. Address reprint requests to Bart A. Ellenbroek, Ph.D., Department of Psycho- neuropharmacology, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Received August 22, 2003; revised October 28, 2003; accepted October 30, 2003. BIOL PSYCHIATRY 2004;55:701–707 0006-3223/04/$30.00 doi:10.1016/j.biopsych.2003.10.024 © 2004 Society of Biological Psychiatry