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Abstract #2239

Muscarinic receptor agonism prevents the functional connectivity aberrancies produced by the psychotogenic drug phencyclidine (PCP)

Carola Canella1,2, Adam Liska1,2, Valentina Piretti1, Alberto Galbusera1, Adam Schwarz3,4, and Alessandro Gozzi1

1Functional Neuroimaging Laboratory, Center for Neuroscience and Cognitive Systems @ Unitn, Istituto Italiano di Tecnologia, Rovereto, Italy, 2CIMeC, Center for Mind/Brain Sciences, University of Trento, Rovereto, Italy, 3Psychological and Brain Sciences, Indiana University, Bloomington, IN, United States, 4Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, United States

NMDA receptor antagonists like ketamine or phencyclidine (PCP) induce robust schizophrenia-like symptoms in rodents via glutamatergic disinhibition of cortico-limbo-thalamic substrates. We show that acute administration of PCP in the mouse elicits aberrant fronto-hippocampal and thalamo-cortical functional connectivity, an effect that can be prevented by pharmacological activation of M1/M4 muscarinic receptors. These changes highlight a previously unreported permissive contribution of muscarinic receptors on the aberrant connectional signatures produced by NMDAr antagonism which bear relevance for human connectivity mapping in hyperglutamatergic states and schizophrenia.

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