AI Article Synopsis
- Lithium can enhance the effectiveness of antidepressants like mirtazapine, but how it works remains unclear.
- A study tested how combining lithium with mirtazapine affects fear behaviors in rats using different brain regions.
- The results showed that using lithium with mirtazapine in the median raphe nucleus (MRN) significantly reduced fear responses, suggesting a specific brain pathway is involved.
Article Abstract
Although preclinical and clinical studies have established the efficacy of lithium augmentation of antidepressant drugs, the mechanism of action of lithium augmentation is not fully understood. Our previous study reported that subchronic lithium treatment enhanced the anxiolytic-like effect of systemic mirtazapine. In the present study, we examined the effect of subchronic lithium in combination with acute local intracerebral injection of mirtazapine on fear-related behaviors in a contextual fear conditioning test in rats to clarify the target brain region of lithium augmentation of mirtazapine. After conditioning by footshock, diet (food pellets) containing Li2CO3 at a concentration of 0.2% was administered for 7 days. Ten min before testing and 7 days after conditioning, mirtazapine (3μg/site) in a volume of 0.5µl was acutely injected into the median raphe nucleus (MRN), hippocampus or amygdala. The combination of subchronic lithium and acute mirtazapine microinjection into the MRN but not the hippocampus or the amygdala reduced fear expression synergistically. These results suggest that intra-MRN mirtazapine treatment with subchronic lithium exerts the anxiolytic-like effect through the facilitation of the MRN-5HT pathway.
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| http://dx.doi.org/10.1016/j.ejphar.2016.05.004 | DOI Listing |
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