RT Journal Article SR Electronic T1 An Adenosine A2A Receptor Antagonist Improves Multiple Symptoms of Repeated Quinpirole-Induced Psychosis JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0366-18.2019 DO 10.1523/ENEURO.0366-18.2019 VO 6 IS 1 A1 Nozomi Asaoka A1 Naoya Nishitani A1 Haruko Kinoshita A1 Yuma Nagai A1 Hikari Hatakama A1 Kazuki Nagayasu A1 Hisashi Shirakawa A1 Takayuki Nakagawa A1 Shuji Kaneko YR 2019 UL http://www.eneuro.org/content/6/1/ENEURO.0366-18.2019.abstract AB Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder characterized by the repeated rise of concerns (obsessions) and repetitive unwanted behavior (compulsions). Although selective serotonin reuptake inhibitors (SSRIs) is the first-choice drug, response rates to SSRI treatment vary between symptom dimensions. In this study, to find a therapeutic target for SSRI-resilient OCD symptoms, we evaluated treatment responses of quinpirole (QNP) sensitization-induced OCD-related behaviors in mice. SSRI administration rescued the cognitive inflexibility, as well as hyperactivity in the lateral orbitofrontal cortex (lOFC), while no improvement was observed for the repetitive behavior. D2 receptor signaling in the central striatum (CS) was involved in SSRI-resistant repetitive behavior. An adenosine A2A antagonist, istradefylline, which rescued abnormal excitatory synaptic function in the CS indirect pathway medium spiny neurons (MSNs) of sensitized mice, alleviated both of the QNP-induced abnormal behaviors with only short-term administration. These results provide a new insight into therapeutic strategies for SSRI-resistant OCD symptoms and indicate the potential of A2A antagonists as a rapid-acting anti-OCD drug.