I C Weiss1, J Feldon. 1. Behavioral Neurobiology Laboratory, ETH, Zurich, Switzerland.
Abstract
RATIONALE: In schizophrenia research, the study of animal models has received considerable attention in the past 20 years. The value of animal models in pre-clinical research is widely recognised, largely because they can provide precious knowledge regarding the neurobiology of schizophrenia and can also be used for developing antipsychotic drugs. Prepulse inhibition (PPI; reduction in startle reflex induced by a prestimulus) is impaired in schizophrenic patients, a finding that has been associated with a loss of sensorimotor gating abilities. In rats, the schizophrenic-like PPI deficit can be induced by pharmacological or surgical manipulations targeting mainly the cortico-meso-limbic circuitry. OBJECTIVES: The literature was critically reviewed in an effort to determine the robustness and the relevance for schizophrenia of another category of animal models, based purely on manipulations of the social environment, that encompasses the neurodevelopmental hypothesis of schizophrenia. Specifically, we focused our attention on the long-term effects of such environmental models on sensorimotor gating processes as assessed in the PPI paradigm, with an attempt to evaluate their face, predictive and construct validity. RESULTS: Our review of the literature leads to the conclusion that social deprivation performed directly after weaning (approximately 21 days of age) is more likely to be a relevant model for PPI impairments in schizophrenia than pre-weaning manipulations. CONCLUSIONS: Although the robustness of such environmental models requires further study, these animal models offer the advantage of avoiding invasive manipulations, which allows for a variety of anatomical, electrophysiological, neuroendocrine or neurochemical investigations in the absence of confounding pharmacological or surgical effects.
RATIONALE: In schizophrenia research, the study of animal models has received considerable attention in the past 20 years. The value of animal models in pre-clinical research is widely recognised, largely because they can provide precious knowledge regarding the neurobiology of schizophrenia and can also be used for developing antipsychotic drugs. Prepulse inhibition (PPI; reduction in startle reflex induced by a prestimulus) is impaired in schizophrenicpatients, a finding that has been associated with a loss of sensorimotor gating abilities. In rats, the schizophrenic-like PPI deficit can be induced by pharmacological or surgical manipulations targeting mainly the cortico-meso-limbic circuitry. OBJECTIVES: The literature was critically reviewed in an effort to determine the robustness and the relevance for schizophrenia of another category of animal models, based purely on manipulations of the social environment, that encompasses the neurodevelopmental hypothesis of schizophrenia. Specifically, we focused our attention on the long-term effects of such environmental models on sensorimotor gating processes as assessed in the PPI paradigm, with an attempt to evaluate their face, predictive and construct validity. RESULTS: Our review of the literature leads to the conclusion that social deprivation performed directly after weaning (approximately 21 days of age) is more likely to be a relevant model for PPI impairments in schizophrenia than pre-weaning manipulations. CONCLUSIONS: Although the robustness of such environmental models requires further study, these animal models offer the advantage of avoiding invasive manipulations, which allows for a variety of anatomical, electrophysiological, neuroendocrine or neurochemical investigations in the absence of confounding pharmacological or surgical effects.