Amelioration of obsessive-compulsive disorder by intracellular acidification of cortical neurons with a proton pump inhibitor

Amelioration of obsessive-compulsive disorder by intracellular acidification of cortical neurons with a proton pump inhibitor

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Abstract Obsessive-compulsive disorder (OCD) is a highly prevalent neuropsychiatric disorder poorly controlled with pharmacological treatment because of the wide variation in symptom patterns.We analysed real-world data on adverse self-reports and here insurance claims to identify a novel therapeutic target for OCD.We found that dopamine D2 receptor (D2R) agonists increased the incidence of OCD-like symptoms, which were suppressed by the concomitant use of proton pump inhibitors (PPIs).Further, OCD-like repetitive and habitual behaviours were observed in mice repeatedly injected with a D2R agonist, quinpirole.However, these abnormalities were suppressed by short-term PPI treatment.

In quinpirole-treated mice, PPI inhibited pyramidal neuron hyperactivity in the lateral orbitofrontal cortex, a region where the P-type proton pump gene Atp4a is abundantly expressed.In primary cultured cortical neurons, short-term PPI treatment lowered intracellular pH and decreased firing activity, which was weleda skin food 75ml best price mimicked by Atp4a knockdown.Our findings show that inhibition of P-type proton pumps may be a novel therapeutic strategy for OCD.