Atypical Antipsychotic Lurasidone Normalizes a Gene Important in Circadian Rhythms
Disruptions to circadian rhythms are common in mood disorders, leading some researchers to believe that normalizing these daily rhythms may improve the illnesses. Several genes, called CLOCK genes, are implicated in circadian rhythms. In animal studies, researcher Marco Riva and colleagues are examining the expression of CLOCK genes in different brain regions as a result of chronic stress that is meant to produce behaviors resembling human depression.
Male rats were exposed to chronic mild stress for two weeks, and divided into those that were susceptible to stress (identified by their loss of interest in sucrose) and those who were not. Then the rats were randomized to receive either a placebo treatment or 3 mg/kg/day of the atypical antipsychotic lurasidone (trade name Latuda), which has been effective in bipolar depression, during five more weeks of the stress procedure.
The researchers observed the expression of clock genes Clock/Bmal1, Per1, Per2, Cry1, and Cry2. In susceptible rats, the chronic mild stress decreased the clock genes Per1, Per2, and Cry2 in the prefrontal cortex. Lurasidone reversed these CLOCK gene abnormalities and the rats’ depression-like behaviors, which may explain some of the drug’s efficacy in bipolar depression.
Editor’s Note: Lurasidone is also a potent inhibitor of 5HT7 serotonin receptors, an effect that has been linked to antidepressant efficacy. Lurasidone also increases brain-derived neurotrophic factor (BDNF), which is important for learning and memory, and prevents stress from decreasing BDNF. Now it seems that lurasidone’s normalization of CLOCK genes may be another mechanism that explains the drug’s antidepressant effects.
