QBI Neuroscience Seminar: Neural mechanisms of MK-801 induced sensitisation
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- Emilia Lefevre
Queensland Brain Institute, University of Queensland
Title: Neural mechanisms of MK-801 induced sensitisation
Abstract: Behavioural sensitisation describes the progressive and enduring augmentation of a response that develops following repeated exposure to a drug. Sensitisation is one mechanism that may account for both the pathophysiology of drug addiction and neuropsychiatric disorders such as schizophrenia. Sensitisation to the NMDA receptor (NMDAR) antagonist MK-801 is a proposed pharmacological model of the glutamatergic -NMDAR hypofunction hypothesis of schizophrenia. In my research I have developed a rat model to explore the neural mechanisms of MK-801 sensitisation. First, I used behavioural techniques to establish the effect of drug dose, environmental context, length of withdrawal period and rat strain on the ability of repeated intermittent MK-801 administration to induce behavioural sensitisation. I then used pharmacological, neurochemical, proteomic and electrophysiological techniques to identify neural mechanisms and adaptations associated with MK-801 sensitisation. In my talk I will elaborate on the role of stress-mediated signaling pathways and changes in synaptic plasticity identified following MK-801 sensitization and how this relates to neuropsychiatric disorders.
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