Grant: Emerging Team Grant: From Genes to Proteins, Cells, Tissues and Patients - LOI

Dysfunctional brain inhibition has been suggested as a mechanism through which symptoms of schizophrenia occur. Brain inhibition refers to a process in which inhibitory neurons reduce excessive brain activity. Excessive brain activity, in turn, has been related to the development of psychotic symptoms in schizophrenia. Several studies suggest that clozapine, one of the most effective treatments in schizophrenia, potentiates brain inhibition through its action on a specific brain receptor, the GABAB receptor. In this proposal we intend to further these promising data through a series of experiments including: (1) molecular experiments to further establish a link between the GABAB receptor and clozapine; (2) animal experiments that will investigate the effects of clozapine on the GABAB receptor in animal models of psychosis; and (3) human experiments intended to determine if the therapeutic effects of clozapine in schizophrenia occur through its action non the GABAB receptor. Collectively, therefore, these experiments intend to evaluate the role of GABAB receptor mediated inhibitory neurotransmission as a potential novel mechanism through which clozapine exerts its unique therapeutic effects in patients with schizophrenia.