An Animal Model of Sensorimotor Gating Deficits in Schizophrenia Predicts Antipsychotic Drug Action

Abstract

Psychiatric researchers have searched for animal models of schizophrenia in order to better understand the neurobiological basis of this group of disorders. Since it is unlikely that a “model” of the entire schizophrenia syndrome can be created, much energy has been devoted to identifying models of specific dysfunctions that characterize schizophrenia patients. Schizophrenia patients are deficient in the normal inhibition of the startle reflex that occurs when the startling stimulus is preceded by a weak prestimulus (Braff et al. 1978, 1992; Braff and Geyer 1990) (Fig. 1A). This loss of normal “prepulse inhibition” (PPI) is thought to be a measure of the deficient sensorimotor gating (Braff and Geyer 1990) that underlies sensory flooding and cognitive fragmentation in these patients (McGhie and Chapman 1961). The neural basis of deficient sensorimotor gating (Swerdlow et al. 1992a) is strikingly consistent with findings from neuroimaging (Wong et al. 1986; Early et al. 1987; Wu et al. 1990) and neuropathological studies (Alishuler et al. 1987, 1990; Pakkenberg 1990; Conrad et al. 1991; Seeman et al. 1984; Bogerts et al. 1985) in schizophrenia patients that have identified abnormalities within limbic cortico-striato-pallido-thalamic (CSPT) circuitry. By elucidating the neural substrates of impaired PPI, it might be possible to gain critical information about the contribution of specific brain abnormalities to sensorimotor gating deficits in schizophrenia patients.