Startle habituation and sensorimotor gating in schizophrenia and related animal models

Studies of the habituation and sensorimotor gating of startle responses to strong exteroceptive stimuli provide some unique opportunities for cross-species explorations into information processing and attentional deficits in schizophrenia. The behavioral plasticity of startle paradigms greatly facilitates the development of animal models of specifiable behavioral abnormalities in schizophrenic patients. This article reviews the promising findings of studies in which measures of startle have been used to clarify the importance of habituation and central inhibition deficits in schizophrenia. In addition, the development of closely related animal models of habituation and sensory gating of startle is discussed. Such animal model studies allow us to make strong inferences about the neurobiological substrate of schizophrenia. Recent evidence from animal studies of prepulse inhibition provides strong support for a schizophrenia-like loss of sensory gating with nucleus accumbens dopamine overactivity. These data are consistent with hypotheses regarding the significance of mesolimbic dopamine overactivity in schizophrenia. New results are also presented from animal model studies of the effects of serotonergic drugs on startle habituation, extending earlier findings of LSD-induced habituation deficits which are similar to those exhibited by schizophrenic patients. These new data indicate that the serotonergic system, working through serotonin-2 receptors, may play a pivotal role in the modulation of startle habituation. The relationship of serotonergic and catecholaminergic mechanisms is also discussed. Collectively, these studies demonstrate the utility of operationally defined measures of preattentive processes in the study of the neurobiological basis of the group of schizophrenias.