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Novel Molecular Targets for Mood Disorders and Psychosis Proceedings of a Workshop (2021) / Chapter Skim
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4 Targeting GABA Receptors to Treat Postpartum Depression
Pages 25-30

The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
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From page 25...
... . • Preclinical studies showed that allopregnanolone analogs improved maternal behavior and pup survival by modulating neural network activity in the basal lateral amygdala (Maguire)
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From page 26...
... Promising results with three more patients prompted SAGE to move forward with two double-blind Phase 3 studies, she said. These studies showed that a 60-hour intravenous infusion of the drug produced a 1  Positive allosteric modulators are drugs that bind to a secondary binding site on a recep tor, causing a conformational change to the primary binding site, leading to enhanced binding affinity for ligands at the primary binding site (Abdel-Magid, 2015)
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From page 27...
... Women who were severely depressed suddenly have affective brightening and relief of horrible symptoms of depression and comorbid anxiety." An oral formulation called zuranolone is also in clinical development for both PPD and major depressive disorder, said Meltzer-Brody. This once-daily tablet does not work as fast as brexanolone, but still produces dramatic results, she said, with an onset of action observed after around 2 days and the full effect seen after about 1 week.
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From page 28...
... Wellner Professor of Neuroscience at the Tufts University School of Medicine, discovered that mice lacking neurosteroid-sensitive GABA receptors exhibit abnormal maternal behaviors as well as behavioral deficits in the postpartum period, with pups suffering increased mortality due to cannibalism or neglect (Maguire and Mody, 2008)
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From page 29...
... . Further studies of the action of neurosteroids on PV interneurons confirmed that allopregnanolone and its synthetic analogs, such as S­ AGE-516, modulate behavioral states and neural network activity in the basal lateral amygdala via the delta subunit of the GABAA receptor on PV interneurons, said Maguire.
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From page 30...
... John Murray, assistant professor of psychiatry, neuroscience, and ­physics at Yale, added that by looking at cell-specific gene expression using single-neuron RNA seq data, it may be possible to identify the pathways involved at the cellular and microcircuit levels, which could help illuminate the paradoxical effects of central nervous system drugs on inhibitory neu rons in certain brain structures. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke, noted that ECT produces a sustained reduction in depressive symptoms similar to what is seen with brexanolone and ­ketamine, suggesting there are circuit changes that respond to the types of short-term neural circuit manipulations that ECT causes.
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Key Terms

  • neural network
  • gaba receptors
  • molecular targets
  • antidepressant effects
  • binding site

  • primary binding
  • neuroactive steroid
  • allosteric modulators
  • lateral amygdala
  • basal lateral

  • positive allosteric
  • network state
  • network states
  • secondary binding
  • gabaa receptor

  • network activity
  • trigger antidepressant
  • ideal level
  • delta subunit
  • tonic inhibition

  • postpartum period
  • pup survival
  • endogenous neuroactive
  • novel formulation
  • maternal behaviors

  • conformational change
  • healthy neural
  • gaba receptor
  • network effects
  • modulate gabaa


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