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

Abstract

Lithium not only has a mood-stabilizing effect but also the augmentation effect of an antidepressant, the mechanism of which remains unclear. Although lithium may augment the effect of mirtazapine, this augmentation has not been confirmed. Using a contextual fear conditioning test in rats, an animal model of anxiety or fear, we examined the effect of subchronic lithium carbonate (in diet) in combination with systemic mirtazapine on the expression of contextual conditioned fear. Mirtazapine (10 mg/kg) reduced freezing one day after fear conditioning dose-dependently, whereas the anxiolytic-like effect of mirtazapine (10 mg/kg) diminished seven days after fear conditioning. When the interval between fear conditioning and testing was seven days, only the combination of subchronic 0.2% Li 2 CO 3 but not 0.05% Li 2 CO 3 with acute mirtazapine (10 mg/kg) reduced freezing significantly. These results indicate that subchronic 0.2% Li 2 CO 3 treatment enhanced the anxiolytic-like effect of systemic mirtazapine. This augmentation therapy might be useful for the treatment of anxiety disorders.

Mirtazapine attenuates anxiety- and depression-like behaviors in rats during cocaine withdrawal

“…Several research studies have suggested that mirtazapine decreases anxiety-like behavior in the EPM and depression-like behaviors in the FST in animals treated with saline (An et al, 2013, 2015, 2016a, 2016b; Kaminska and Rogoz, 2016; Rogóż, 2010, 2012; Rogóż et al, 2012). We found similar results: in animals dosed with 30 mg mirtazapine, anxiety-like (as measured in the EPM test, OFT and the LDT) and depression-like behaviors (according to the FST) decreased after 15 days of treatment.…”

Mirtazapine exerts an anxiolytic-like effect through activation of the median raphe nucleus-dorsal hippocampal 5-HT pathway in contextual fear conditioning in rats

“…Acute systemic administration of selective serotonin (5-HT) reuptake inhibitors (SSRIs) and 5-HT 1A receptor agonists before re-exposure to the footshock chamber reduces the expression of CFC, an anxiolytic-like effect (for a review, see Inoue et al, 2011). Moreover, systemic administration of mirtazapine, a noradrenergic and specific serotonergic antidepressant, reduces the expression of CFC and increases extracellular 5-HT levels in the DH but not the prefrontal cortex (Kakui et al, 2009;Yamauchi et al, 2012;An et al, 2015). The anxiolytic-like effect of systemic mirtazapine was reversed by a selective 5-HT 1A receptor antagonist, WAY-100635 (Kakui et al, 2009).…”