Dual modes of extracellular serotonin changes in the rat ventral striatum modulate adaptation to a social stress environment, studied with wireless voltammetry
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The role of serotonin in stress and anxiety, particularly in social environments, is not well understood. Selective serotonin reuptake inhibitors are useful for patients that experience social anxiety; however, their mechanism of action has not been fully characterized. Dopamine is known to operate in different temporal modes (fast phasic, intermediate, and tonic changes). We hypothesized that serotonin may also operate in temporal modes in the context of social stress. We used wireless voltammetry (4 Hz) to investigate changes in extracellular ventral striatal serotonin and dopamine during a test of repeated social interactions between two rats. Test rats (electrode-implanted; n = 5) and counter rats (n = 6) were placed in separate sections of a partitioned box. The partitions were raised to allow interactions for 10 min; four sessions were repeated at 10-min intervals. In the first session, serotonin increased gradually, then peaked at approximately the end of the interaction, and decreased rapidly between sessions. This slow phasic increase in serotonin diminished gradually (but significantly) in subsequent interactions. Test rats received active, one-sided contacts (chasing, walking-over, and occasional attacking behavior) from counter rats. Changes in contact times were not correlated with changes in phasic serotonin increases. Dopamine levels did not increase. Citalopram caused significant suppression of slow phasic increases, caused tonic increases in basal serotonin concentrations, and caused active (chasing, all grooming), but not aggressive behavior in test rats. These findings implied that the slow phasic serotonin increase in the ventral striatum induced adaptation to social stress caused by a counter rat; moreover, the tonic increase in serotonin promoted the adaptive change and caused socially dominant behavior.
KeywordsSerotonin Social stress Accumbens Anxiety Obsessive–compulsive disorder Habituation
This study was supported by two Grants-in-Aid for Scientific Research: No. 17650095 (Hoga-Kenkyu) and No. 17075002 (“Mobiligence” Project on Priority Areas: Emergence of Adaptive Motor Function through Interaction between Body, Brain and Environment) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. We would like to thank the former Professor Shigeru Kitazawa, Department of Physiology, Juntendo University School of Medicine (Department of Physiology, Osaka University Faculty of Medicine, Osaka), for his helpful discussions and suggestions; Professor Kaoru Takakusaki, Asahikawa Medical University (Asahikawa City, Japan), for his encouraging discussions; and Dr. Masaki Nakatani, the Director of Sumiyoshi Hospital (Kofu City, Japan), for his clinical discussions. The wireless voltammetry system was developed with the technical support of Dr. Akitane Akiyama of Rainbow Science (Yokohama, Japan), Mr. Yasuo Udagawa of Data Graph Co. Ltd (Tokyo, Japan), Dr. Maki Kagohashi (Juntendo University, Neurology), and Dr. Shunjiro Moizumi (Juntendo University, Physiology). The carbon fiber was kindly donated by Toho Tenax Co. (Tokyo, Japan). Finally, we thank Ms. Chihiro Nakazato for her helpful assistance.
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