The Contraceptive Agent Provera Enhances GABAA Receptor-Mediated Inhibitory Neurotransmission in the Rat Hippocampus: Evidence for Endogenous Neurosteroids?

  title={The Contraceptive Agent Provera Enhances GABAA Receptor-Mediated Inhibitory Neurotransmission in the Rat Hippocampus: Evidence for Endogenous Neurosteroids?},
  author={Delia Belelli and Murray B. Herd},
  journal={The Journal of Neuroscience},
  pages={10013 - 10020}
Neurosteroids typified by 5α-pregnan-3α-ol-20-one (5α3α) have emerged as the most potent endogenous positive modulators of the GABAA receptor, the principal mediator of fast inhibitory transmission within the CNS. Neurosteroids can be synthesized de novo in the brain in levels sufficient to modulate GABAA receptor function and, thus, might play an important physiological-pathophysiological role. Indirect support for this proposal comes from the observation that neurosteroid action is region and… 

Figures and Tables from this paper

Physiological roles of endogenous neurosteroids at α2 subunit-containing GABAA receptors
The α2Q241M knock-ins showed greater anxiety levels in two classical rodent anxiety paradigms, consistent with endogenous neurosteroids mediating anxiolysis via α2-type GABAA receptors, which would identify the α2 isoform as an appropriate target for generating receptor subtype-selective neurosteroid therapeutics for anxiety disorders.
Brain neurosteroids are natural anxiolytics targeting α2 subunit γ-aminobutyric acid type-A receptors
It is revealed that α2-GABAAR targeting neurosteroids may act as selective anxiolytics for the treatment of anxiety disorders, providing new therapeutic opportunities for drug development.
Neurosteroids, GABAA receptors and neurosteroid based drugs: are we witnessing the dawn of the new psychiatric drugs?
The purpose of this review paper is to analyze recent research in the field of neurosteroids and neurosteroid-based drugs with emphasis on interaction of Neurosteroids with brain GABAA receptors and the therapeutic potential of GAMS, GAMSA, and TSPO activators.
Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites
Two discrete binding sites in the GABAA receptor’s transmembrane domains are identified that mediate the potentiating and direct activation effects of neurosteroids and provide a unique opportunity for the development of new therapeutic, neurosteroid-based ligands and transgenic disease models of Neurosteroid dysfunction.
Neurosteroid: Molecular Mechanisms of Action on the GABAA Receptor
The molecular mechanisms underpinning the non-genomic effect of agonist and antagonist neurosteroids will be discussed with particular emphasis being given to the role of GABA A receptor isoforms.
Brain Steroidogenesis Mediates Ethanol Modulation of GABAA Receptor Activity in Rat Hippocampus
It is shown that ethanol increases the concentration of 3α,5α-THP as well as the amplitude of GABAA receptor-mediated IPSCs recorded from CA1 pyramidal neurons in isolated hippocampal slices, suggesting that ethanol may modulate GabAA receptor function through an increase in de novo neurosteroid synthesis in the brain that is independent of the HPA axis.
Neurosteroids: Endogenous allosteric modulators of GABAA receptors
Neurosteroids and GABA-A Receptor Function
Molecular mechanisms underlying neurosteroid action on the GABAA-receptor, mood changes, and cognitive functions are described.


Does neurosteroid modulatory efficacy depend on GABAA receptor subunit composition?
A direct activation of Cl- current by 3 alpha-OH-DHP was observed in native and recombinant receptors but its efficacy on the various molecular forms of GABAA receptor tested was always smaller than that of identical concentrations (10 microM) of GABA.
Anticonvulsant steroids and the GABA/benzodiazepine receptor-chloride ionophore complex
Neurosteroids and GABAA receptor function.
Enhanced Neurosteroid Potentiation of Ternary GABAAReceptors Containing the δ Subunit
The results suggest that the GABAA receptor δ subunit confers increased sensitivity to neurosteroid modulation and that the intrinsic gating and desensitization kinetics of α1β3δ GAB AA receptors are altered by THDOC.
Oxytocin Regulates Neurosteroid Modulation of GABAAReceptors in Supraoptic Nucleus around Parturition
It is found that, during parturition, the GABAARs become insensitive to the neurosteroid allopregnanolone attributable to a shift in the balance between the activities of endogenous Ser/Thr phosphatase and PKC, indicating that there may be an inverse causal relationship between the extent to which the GABAAR or one of its interacting proteins is phosphorylated and the Neurosteroid sensitivity of the GABA AR.