Cuprizone short-term exposure: Astrocytic IL-6 activation and behavioral changes relevant to psychosis

•One-week cuprizone exposure in mice causes unique deficits•Exposure elicits hypersensitivity to psychostimulants and cognitive deficits•Astrocyte and microglia dysregulation is induced without signs of demyelination•Exposure significantly upregulates interleukin-6 in astrocytes

A growing body of evidence suggests the involvement of inflammatory processes in the pathophysiology of schizophrenia. Four- to 8-week exposure to cuprizone, a copper chelator, causes robust demyelination and has been used to build a model for multiple sclerosis. In contrast, we report here the effects of 1-week cuprizone exposure in mice. This short-term cuprizone exposure elicits behavioral changes that include augmented responsiveness to methamphetamine and phencyclidine, as well as impaired working memory. The cellular effects of 1-week cuprizone exposure differ substantially from the longer-term exposure; perturbation of astrocytes and microglia is induced without any sign of demyelination. Furthermore, the proinflammatory cytokine interleukin-6 was significantly up-regulated in glial fibrillary acidic protein (GFAP)-positive cells. We propose that this cuprizone short-term exposure may offer a model to study some aspects of biology relevant to schizophrenia and related conditions.