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Abstract #1535

Antibiotic Minocycline Suppressess the PhMRI Response to Acute Ketamine Challenge

Duncan Jack Hodkinson1, Diana Cash2, Steve C. R. Williams2, Shane McKie3, John Francis W. Deakin3, Steve R. Williams1

1Imaging Science & Biomedical Engineering, University of Manchester, Manchester, United Kingdom; 2Neuroimaging Research Group, Institute of Psychiatry, King's College London, London, United Kingdom; 3Neuroscience & Psychiatry Unit, University of Manchester, Manchester, United Kingdom

Minocycline is a safe, widely prescribed antibiotic which has beneficial effects against apoptosis, inflammation, and microglial activation. Increasing clinical evidence suggests minocycline improves negative symptoms in schizophrenia if added adjunctively to usual therapy. However, the precise neuropharmacological mechanisms underlying these effects remain to be fully elucidated. Here, we applied pharmacological MRI (phMRI) to investigate the modulatory effects of minocycline on regional BOLD signal changes induced by acute ketamine challenge in the rat brain. Pre-treatment with minocycline (50mg/kg s.c.) produced widespread inhibition of ketamine-induced functional activation. These findings suggest direct involvement of minocycline in modulating glutamate neurotransmission.