Inhibition of Fatty Acid Amide Hydrolase Alters Cortical CREB Signaling and Social Behavior in a Rat Model of Schizophrenia
European Journal of Neuroscience February 1, 2026 Aditya R. Kumar, Lenka Seillier, Martin Kuchař et al.
In a rat model of schizophrenia-like social withdrawal, an inhibitor of fatty acid amide hydrolase (FAAH) called URB597 reversed social deficits caused by the drug phencyclidine (PCP), but reduced social interaction in healthy control rats. The study measured CREB protein and its activated form pCREB across six cortical brain regions. Most regions showed little change, but the agranular insular cortex (AI) exhibited distinct effects: pCREB levels in the AI were reduced by both PCP and URB597 in controls, and pCREB in this region correlated positively with social interaction time. The findings identify the AI as a key brain area for social withdrawal and suggest that targeting the endocannabinoid system there may offer a therapeutic strategy for schizophrenia's negative symptoms.