title: Effect of the coadministration of citalopram with mirtazapine or atipamezole on rat contextual conditioned fear.
abstract: BACKGROUND
  Mirtazapine, a noradrenergic and specific serotonergic antidepressant, which blocks the α2-adrenergic autoreceptors and heteroreceptors, has shown anxiolytic properties in clinical trials and preclinical animal experiments. The addition of mirtazapine to selective serotonin reuptake inhibitors (SSRIs) is clinically suggested to be more effective for anxiety disorders. In this study, we examined the combined effects of mirtazapine and citalopram, an SSRI, on the freezing behavior of rats, which was induced by contextual conditioned fear as an index of anxiety or fear.
  
  
  METHODS
  Male Sprague Dawley rats individually received footshocks in a shock chamber, and 24 hours later, they were given citalopram and/or mirtazapine injections. One hour after citalopram and 30 minutes after mirtazapine administration, freezing behavior was analyzed in the same shock chamber without shocks.
  
  
  RESULTS
  Mirtazapine decreased freezing in a dose-dependent manner, which is consistent with a previous report; it also enhanced an anxiolytic-like effect at a high dose (30 mg/kg) of citalopram. Because mirtazapine blocks α2-adrenoreceptors, the combined effect of atipamezole, a selective α2 receptor antagonist, with citalopram was also examined. Similar to mirtazapine, atipamezole reduced freezing dose-dependently, but the enhancement of citalopram's effects by atipamezole was not clear when compared with mirtazapine.
  
  
  CONCLUSIONS
  The present findings suggest that mirtazapine has an anxiolytic-like effect and may enhance the anxiolytic-like effect of SSRIs, but this enhancement may not be explained by its anti-α2 property alone.
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan ; Medical Affairs, Dainippon Sumitomo Pharma, Co, Ltd, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
authors.forename: Yan
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan ; Regenerative and Cellular Medicine Office, Dainippon Sumitomo Pharma, Co, Ltd, Osaka, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Takamura
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nakagawa
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kitaichi
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Koyama
authors.affiliation: Department of Psychiatry, Hokkaido University Graduate School of Medicine, Sapporo Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kusumi
keywords: anxiety; conditioned fear; mirtazapine; selective serotonin reuptake inhibitor; α2-adrenoreceptor