Basic information

Investigator: Alexandre Seillier, Ph.D.
Main recipient: National Institute of Mental Health (NIMH)
Research period: 1/1/2022 - 31/12/2024
Total budget: 9,341,000 CZK
Supported by: Czech Science Foundation (GAČR)

Annotation

The negative symptoms of schizophrenia account for a large part of the long-term disability and poor functional outcomes in patients with schizophrenia and remain an unmet therapeutic need. Therefore, it is paramount to understand the pathophysiology of these debilitating symptoms, identify novel pharmacological targets and translate this knowledge into new therapies. Using an animal model for schizophrenia, we have previously demonstrated that social withdrawal, one of the core negative symptoms of the disease, resulted from a lack of cannabinoid CB1 receptor stimulation. We have also identified the orbitofrontal cortex as a potentially relevant anatomical substrate for social withdrawal and, equally important, its reversal by cannabinoids. In this project, we will combine in vivo electrophysiology and behavioral pharmacology (including local micro-infusion), together with ex-vivo neurochemical and molecular approaches, to elucidate whether social withdrawal stems from a dysfunctional orbitofrontal endocannabinoid transmission.