Anxiolytic-like profile of mirtazapine in rat conditioned fear stress model: Functional significance of 5-hydroxytryptamine 1A receptor and α1-adrenergic receptor

Combined treatment with subchronic lithium and acute intracerebral mirtazapine microinjection into the median raphe nucleus exerted an anxiolytic-like effect synergistically

“…Behavioral animal studies have confirmed that systemic administration of mirtazapine also exerts an anxiolytic-like effect in rats Kakui et al, 2009), which represents supporting clinical evidence of the efficacy of mirtazapine treatment for anxiety disorders (Bandelow et al, 2008). In addition, Yamauchi et al (2012) found that systemic administration of mirtazapine increases extracellular 5-HT levels in the dorsal hippocampus but not in the prefrontal cortex.…”

“…Therefore, the study was designed to assess the effectiveness of subchronic lithium with acute local mirtazapine treatment in the MRN, hippocampus and amygdala in rats using the contextual fear conditioning test as an animal model of anxiety. Mirtazapine, which is an α 2 -adrenergic antagonist, is considered to stimulate serotonergic neuronal firing through the stimulation of noradrenergic neurons in the MRN and by increasing the extracellular 5-HT levels in the forebrain Kakui et al, 2009;Millan, 2006;Yamauchi et al, 2012).…”

Serotonin Noradrenaline Reuptake Inhibitors (SNRIs)

“…A potential anxiolytic-like profile of mirtazapine in rat conditioned fear stress model was investigated. It was reported that the anxiolytic-like action of mirtazapine involves activation of 5-HT1A receptor and alpha1 adrenoceptor to different extents, and are compatible with one aspect of mirtazapine's pharmacological profile (Kakui et al, 2009). …”

Subchronic lithium treatment increases the anxiolytic-like effect of mirtazapine on the expression of contextual conditioned fear

“…The doses of mirtazapine used in this study were based on previous reports (Kakui et al, 2009; the company's drug information). The dose of mirtazapine (10 mg/kg) used in this study produces plasma mirtazapine concentrations that are comparable to or greater than the clinically therapeutic plasma concentrations observed after administration of the clinically maximal dose (45 mg/day) of mirtazapine (company's drug information).…”

“…In addition, animal behavioral studies have shown that systemic administration and local administration to the median raphe nucleus of mirtazapine decreased contextual conditioned freezing behavior, an index of fear or anxiety Kakui et al, 2009). An in vivo microdialysis study reported that mirtazapine increased extracellular 5-HT concentrations in the hippocampus of rats (Yamauchi et al, 2012).…”