Reduced synaptophysin immunoreactivity in the dentate gyrus of prepulse inhibition-impaired isolation-reared rats

Isolation rearing of rat pups from weaning produces neurochemical and behav ioural changes that may have relevance to the neurodevelopmental basis of n europsychiatric disorders such as schizophrenia. Although limited, studies have begun to probe for neuroanatomical changes produced by isolation reari ng. In the present study, rat pups were reared in isolation, i.e., housed o ne per cage, from weaning. After 8 weeks of isolation, 'isolates' were comp ared to their socially reared controls (housed three per cage) in two behav ioural paradigms: locomotor activity in a novel open field and prepulse inh ibition (PPI) of the acoustic startle response. Subsequently, all rats were sacrificed and their brains removed. The hippocampus was sectioned and ana lysed immunohistochemically using an antibody to the synapse-specific prote in synaptophysin, to gain an estimate of the synaptic content of selected h ippocampal subfields. Isolates demonstrated locomotor hyperactivity and def icits in PPI relative to socially reared controls. Analysis of synaptophysi n immunoreactivity suggested that isolates had significantly reduced synapt ic content in the hippocampal dentate gyrus molecular layer, with smaller, non-significant reductions in the CA1 and CA3 regions. This pattern of chan ge may be consistent with reduced neuronal input to the dentate gyrus via t he entorhinal cortex, suggesting developmental changes in hippocampal-corti cal circuitry. These preliminary studies extend the characterisation of iso lation oaring as a model for the investigation of neurodevelopmental diseas es such as schizophrenia. (C) 1999 Elsevier Science B.V. All rights reserve d.