title: Involvement of adenosine A2A receptors in depression and anxiety.
abstract: When administered to normal healthy patients, a nonselective adenosine A1/A2A antagonist, caffeine, tended to improve anxiety and depression at low doses and to exacerbate anxiety at high doses. Caffeine also appears to enhance anxiety-related symptoms in patients with panic disorder, and A2A receptor-deficient mice have been reported to exhibit higher anxiety-like behaviors, as well as a lower incidence of depression-like behaviors. Some selective A2A antagonists were reported to ameliorate anxiety-like behaviors in rodents, while others did not affect these behaviors. In addition, most A2A antagonists showed inhibitory effects on depression-like behaviors. The mechanisms underlying the relationship between A2A receptor antagonists and anxiety and depression remain unclear at the present time, although many studies have produced hypotheses. Given that a selective A2A receptor antagonist has recently become available for use in humans, research on the role of A2A receptors in the treatment of mental illness should progress in the near future.
authors.affiliation: Central Nervous System Research Laboratories, CNS R&D Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan. Electronic address: kohji.yamada@kyowa-kirin.co.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Central Nervous System Research Laboratories, CNS R&D Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Central Nervous System Research Laboratories, CNS R&D Unit, R&D Division, Kyowa Hakko Kirin Co., Ltd., Shizuoka, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kanda
mesh_terms: D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D043705:Receptor, Adenosine A2A / Q000378:metabolism*
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D002110:Caffeine
keywords: Adenosine A(2A) receptors; Antagonist; Anxiety; Behavior; Depression; Istradefylline; Mental illness; Rodents