Developmental markers of psychiatric disorders as identified by sensorimotor gating.

Abstract

Prepulse inhibition (PPI) of the acoustic startle reflex is an operational measure of sensorimotor gating that is amenable to cross-species comparisons. Deficits in PPI have been repeatedly reported in patients with schizophrenia or other psychiatric disorders characterized by abnormalities in sensory, cognitive, or motor gating. Because some forms of schizophrenia appear to be attributable to early developmental perturbations, many animal studies have examined the influences of various developmental manipulations on PPI in adulthood. For example, isolation rearing of rats from weaning into adulthood leads to a reorganization of brain circuitry including changes in monoamine systems that modulate PPI. Isolation rearing of rats leads to deficits in PPI that are not evident pre-puberty, are enduring in adulthood, and are developmentally specific, in that isolation of adult rats does not affect PPI. The PPI deficits in isolation-reared rats are reversed by typical or atypical antipsychotic treatments, including raclopride, haloperidol, clozapine, olanzapine, quetiapine, and even the putative antipsychotic M100907. In contrast, other psychoactive drugs, such as chlordiazepoxide, diazepam, prazosin, or amitriptyline, do not normalize PPI in isolation-reared rats. Hence, the isolation-rearing model may help identify novel antipsychotics. Thus, social isolation rearing of rats provides a developmentally specific, non-pharmacological manipulation that leads to deficits in sensorimotor gating that mimic those observed in schizophrenia patients and are responsive to antipsychotic medications.