[Biological basis of anxiety disorders and serotonergic anxiolytics].
Selective serotonin reuptake inhibitors (SSRIs) have wide indications for the treatment of anxiety disorders, including panic disorder, generalized anxiety disorder, posttraumatic stress disorder, obsessive-compulsive disorder and social anxiety disorder in addition to depression. Until recently, no animal model has been available for screening the anxiolytic effect of SSRIs and studying its mechanism of action. We have investigated the relationship between serotonin neurotransmission and anxiety using conditioned fear stress (CFS), an animal model of anxiety. CFS increased serotonin neurotransmission in the medial prefrontal cortex and amygdala. In behavioral pharmacological studies, SSRIs, serotonin1A agonists and monoamine oxidase inhibitors, which are assumed to facilitate serotonin neurotransmission, decreased conditioned freezing, an index of anxiety or fear, in CFS. In vivo microdialysis studies showed that serotonin neurotransmission in the medial prefrontal cortex increased after recovery from the freezing behavior. Microinjection of SSRI to the basolateral nucleus of the amygdala reduced conditioned freezing, indicating that the amygdala is one of target brain sites of anxiolytic action of SSRIs. Furthermore, CFS-induced c-Fos expression in the basolateral nucleus of the amygdala was reduced by SSRI pretreatment. Taken together, recent studies indicate that facilitation of brain serotonin neurotransmission decreases anxiety in agreement with the clinical evidence.
Inoue
Takeshi
T
Department of Psychiatry, Neural Function, Hokkaido University Graduate School of Medicine, Kita 15, Nishi 7, Kita-ku, Sapporo, 060-8638 Japan.
Izumi
Takeshi
T
Li
Xiao-Bai
XB
Huang
Ji Zhong
JZ
Kitaichi
Yuji
Y
Nakagawa
Shin
S
Koyama
Tsukasa
T
D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy*; D001921:Brain / Q000378:metabolism; D003863:Depression / Q000188:drug therapy; D005239:Fear / Q000187:drug effects; D051379:Mice; D018377:Neurotransmitter Agents / Q000502:physiology; D016584:Panic Disorder / Q000188:drug therapy; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy
D018377:Neurotransmitter Agents; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors