Allopregnanolone is a selective activator of GABA-A receptor with the concentration of 10 nM [1].
GABA-A receptor is a pentameric transmembrane receptor and sits in the membrane of neuron. As a subtype of receptor for the neurotransmitter GABA, GABA-A receptor mediates the bulk of synaptic inhibition in the central nervous system and prevents action potential generation by short-circuiting the depolarization produced by excitatory neurotransmission. It has been shown that allopregnanolone can directly activate GABA-A receptor and it also can allosteric enhance GABA-evoked currents to function [2] [1].
Allopregnanolone is an agonist for GABA-A receptor. When tested with rat retinas exposed to hydrostatic pressure (75 mm Hg) for 24 hours, administration of alloprenanolone significantly suppressed pressure-induced axonal swelling via functioning on GABA-A R in a dose-dependent manner [1].
In spinal cord slides from na?ve rats, pre-incubation with TGOT significantly lower the following allopregnanolone (0.11 ± 0.04 ng/mg) treatment thus decayed GABA-A R which resulted in the spinal neurosteroidogenesis [3].
It is also reported that subcutaneously injected allopregnanolone to male Wistar rats once daily over five consecutive days resulted in energy intake and weight gain increasement [4].
References:
[1]. Ishikawa, M., et al., Neurosteroids are endogenous neuroprotectants in an ex vivo glaucoma model. Invest Ophthalmol Vis Sci, 2014. 55(12): p. 8531-41.
[2]. Maguire, J. and I. Mody, Steroid hormone fluctuations and GABA(A)R plasticity. Psychoneuroendocrinology, 2009. 34 Suppl 1: p. S84-90.
[3]. Juif, P.E., et al., Long-lasting spinal oxytocin analgesia is ensured by the stimulation of allopregnanolone synthesis which potentiates GABA(A) receptor-mediated synaptic inhibition. J Neurosci, 2013. 33(42): p. 16617-26.
[4]. Holmberg, E., et al., Repeated allopregnanolone exposure induces weight gain in schedule fed rats on high fat diet. Physiol Behav, 2015. 140: p. 1-7.