In a study recently published in PNAS, Dr. Jing-Ning Zhu’s group in Nanjing University reports that a glutamatergic neuronal circuitry from the prelimbic prefrontal cortex (PrL) to the nucleus accumbens (NAc) core is responsible for co-occurrence of anxiety- and obsessive-compulsive-like behaviors. Notably, activation of the histamine presynaptic H3 heteroreceptor localized in the PrL-NAc glutamatergic terminals ameliorates stress-induced anxiety and obsessive-compulsive-like behaviors.