Brief ReportsRegulation of Phosphorylation of Cyclic AMP Response Element-Binding Protein by Paroxetine TreatmentsMorinobu, Shigeru*; Russel, David S.‡; Sugawara, Sachiko*; Takahashi, Michihiro‡; Fujimaki, Koichiro†Author Information *Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, Hiroshima; †Department of Psychiatry, Shiga University of Medical Science, Shiga, Japan; and ‡Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, Connecticut, USA Address correspondence and reprint requests to Shigeru Morinobu, Department of Psychiatry and Neurosciences, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. Clinical Neuropharmacology: March-April 2000 - Volume 23 - Issue 2 - p 106-109 Buy Abstract The present study was undertaken to examine the effect of paroxetine, a selective serotonin reuptake inhibitor, on the phosphorylation of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) in the rat brain. Single administration of paroxetine significantly induces the phosphorylation of CREB in the rat frontal cortex and hippocampus in a time-dependent manner. Repeated administration of paroxetine attenuates CREB phosphorylation in response to acute paroxetine challenge. These findings suggest that the enhancement of intracellular signal transduction after the activation of serotonin receptors may be attenuated after chronic paroxetine treatment, and this attenuation may be, at least in part, involved in the therapeutic efficacy of paroxetine. © 2000 Lippincott Williams & Wilkins, Inc.