PS140. Suppression of reward-induced dopamine release in the nucleus accumbens of the chronic mild stress model rats

One of the main symptoms of major depressive disorder is an inability to experience pleasure, anhedonia. Dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) constitute the brain reward system. Various kinds of rewards and drugs of abuse elevate the dopamine (DA) release in the NAc, which is considered to be important to generate pleasant emotion. In the animal models of depression, sucrose preference is reported to be reduced, and this reduction is thought to be due to the suppression of VTA dopaminergic neurons. In this study, using a chronic mild stress (CMS) model which is one of the animal models of depression, we examined the influence of CMS on reward-induced DA release in the NAc and the effect of SSRI treatment on the alteration of DA release induced by CMS. Male Sprague-Dawley rats (4 week old at the start of CMS) were exposed to CMS for 4 weeks. Then, escitalopram (10 mg/kg/day) or vehicle was intraperitoneally administered for 3 weeks. Extracellular DA levels in the NAc were measured using an in vivo microdialysis technique, and reward (30% sucrose water)-induced DA release was examined. In the non-CMS groups, the reward elevated extracellular DA levels regardless of presence or absence of SSRI treatment. In the CMS group without SSRI treatment, the reward-induced DA release disappeared. Chronic treatment with escitalopram recovered the reward-induced DA release in the CMS group. These results suggest the possibility that the reward-induced DA release in the NAc is useful for an index to quantitatively evaluate the anhedonic condition and the effect of SSRI treatment. PS141 Depressive Symptoms, as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1 Yuki Murakami1, 2 *, Eiichi Tomita3, Makiya Nishikawa4, Akihiro Mouri5, Hisako Kubo1, Yasuko Yamamoto1,6, Hyoung-Chun Kim7, Toshitaka Nabeshima5 and Kuniaki Saito1, 5, 6 1 Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, Kyoto 606–8507, Japan. 2 Organization for Research Initiatives and Development, Doshisha University, Kyoto 610-0394, Japan. 3 Department of Gastroenterology, Gifu Municipal Hospital, Gifu 500–8513, Japan. 4 Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606–8501, Japan. 5 Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi 470–1192, Japan. 6 Department of Disease Control and Prevention, Fujita Health University Graduate School of Health Sciences, Toyoake, Aichi 470–1192, Japan. 7 Neuropsychopharmacology & Toxicology Program, College of Pharmacy, Kangwon National University, Gangwon 200–701, Republic