Psychopharmacology of Anxiety and Depression : Anxiolytic effect of SSRI and an animal model of anxiety(Bases and Clinical Practice of Anxiety and Depression)

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  • 不安と抑うつの精神薬理 : SSRIの抗不安作用と不安の動物モデル(不安と抑うつの基礎と臨床)(第37回日本心身医学会総会)
  • 不安と抑うつの精神薬理--SSRIの抗不安作用と不安の動物モデル
  • フアン ト ヨクウツ ノ セイシン ヤクリ SSRI ノ コウ フアン サヨウ

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Abstract

Recent clinical evidence has shown that selective serotonin reuptake inhibitors (SSRls) are effective in the treatment of various anxiety disorders, such as panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder and social phobia in addition to depressive disorders. However, several animal models of anxiety, such as conflict test, have failed to show the anxiolytic effects of SSRI. Conditioned fear stress (CFS : re-exposure to an environment paired previously with inescapable electric footshock) induces defecation, urination, increased blood pressure and freezing behavior, an index of anxiety. The authors have shown the anxiolytic effects of benzodiazepines, SSRls, serotonin_<lA> (5-HT_<IA>) agonist and 5-HT precursor on CFS-induced freezing behavior. These results are consistent with clinical effects of these drugs in the treatment of anxiety disorders, and suggest that facilitation of 5-HT neurotransmission decreases anxiety because SSRIs and 5-HT precursor are assumed to increase the output from the 5-HT synapse. We also reported that CFS increased the serotonergic activity in the medial prefrontal cortex (mPFC). Furthermore, more intense CFS, following repeated conditioning, increased it not only in the mPFC, but also in the nucleus accumbens and amygdala. The bilateral mPFC Iesions did not reduce conditioned freezing. This lesion study and other previous reports suggest that 5-HT activation in the mPFC during CFS does not cause emotional reaction to CFS, but may, rather, reflect coping with stress. These findings suggest the close relationship between anxietv and serotonin in the brain.

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