Anxiolytic-like effect of mirtazapine mediates its effect in the median raphe nucleus.
Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA), blocks the α2-adrenergic autoreceptors and heteroreceptors, which are responsible for controlling noradrenaline and 5-hydroxy-tryptamine (5-HT) release. Though preclinical and clinical studies have shown that mirtazapine exerts an anxiolytic action, its precise brain target sites remain unclear. In the present study, we investigated the brain area(s) in which mirtazapine exerts its anxiolytic-like effects on the expression of contextual conditioned freezing in rats. Mirtazapine (3 μg/site) was directly injected into three brain structures, the median raphe nucleus (MRN), hippocampus and amygdala. Freezing behavior tests were carried out 10 min after injections. Our results showed that the intra-MRN injection of mirtazapine reduced freezing significantly, whereas injections into the hippocampus or the amygdala did not. In addition, the intra-MRN injection of mirtazapine did not affect locomotor activity. These results suggest that the anxiolytic-like effect of mirtazapine might be mediated by its action on the MRN.
Yan
Y
An
Takeshi
T
Inoue
Yuji
Y
Kitaichi
Takeshi
T
Izumi
Shin
S
Nakagawa
Ning
N
Song
Chong
C
Chen
XiaoBai
X
Li
Tsukasa
T
Koyama
Ichiro
I
Kusumi
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000679:Amygdala / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological; D005239:Fear / Q000502:physiology* / Q000523:psychology; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D009043:Motor Activity / Q000187:drug effects; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; D008803:Mianserin; D000078785:Mirtazapine