How Do Antidepressants Work Longer?

New research led by neuroscientists identified the role of brain-derived steroids as mood regulators in rodent models during and after pregnancy. It also helps to understand the episodic nature of many mood disorders.

The prolonged antidepressant effects of allopregnanolone, a neuroactive steroid used to treat postpartum depression, may involve the ability of the compound to modify communication in an area of the brain important for mood and emotion regulation.

Sage Therapeutics developed brexanolone, its proprietary formulation of a naturally produced neurosteroid called allopregnanolone. The drug became the first to receive FDA approval for the treatment of postpartum depression in adults.

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‘Antidepressant drugs have prolonged effects due to alteration in brain network and behavioral deficits.’

In clinical trials, one 60-hour intravenous infusion of brexanolone demonstrated a significant and clinically meaningful mean reduction in symptoms of postpartum depression within 60 hours that was maintained for up to 30 days.

In a study recently published in Biological Psychiatry, researchers from Tufts University School of Medicine and Sage examined the effect of a single treatment of allopregnanolone in mice to understand how the compound can induce long-lasting effects on mood in the treatment of postpartum depression.

“We were really struck by the persistent antidepressant effects of the medication in the clinical trials, which long outlasted the treatment exposure. These prolonged effects were not well explained by the known mechanisms of action of these compounds,” said Maguire, senior and corresponding author and a Kenneth and JoAnn G. Wellner Professor at Tufts School of Medicine.

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Oscillations occur when brain cells fire together in a specific rhythm or frequency and represent local and long-range communication in the brain. Specific frequencies of oscillations in the brain are associated with different behavioral states, like sleeping and waking.

However, in neuropsychiatric disorders like depression and post-traumatic stress, oscillations can be disturbed in areas like the basolateral amygdala, potentially leading to symptoms.

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In the current study, the researchers found that long-term alterations in network state in the basolateral amygdala following chronic stress is a major risk factor for psychiatric illnesses.

By recording brain oscillations in humans and rodents, researchers demonstrated that direct application of the drug in the basolateral amygdala can improve behavior in mice.

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This suggests that this area is important in mediating the acute effects of the drug as well as the long-term changes in the brain and behavioral states.

“Our results may provide an essential framework for understanding the role of oscillations and associated behavioral states,” said Maguire, who is also a member of the neuroscience and MS in Pharmacology & Drug Development program faculty at Tufts Graduate School of Biomedical Sciences.

Though there are many mechanisms involved in altering the brain’s network state, changing oscillations in the brain can lead to long lasting changes in behavior, this both adds to our understanding of the brain and may be a new strategy for drug therapies.

Source-Medindia