Effect And Mechanism Of Pregnanolone On Discharge Rate Of Rat Suprachiasmatic Nucleus Neurons And Habenular Nucleus Neurons In Vitro

In 1984, a potent and selective interaction of the neuroactived steroid with the GABAa receptor was demonstrated. Subsequent studies established that certain naturally occurring steroids were potent positive allosteric modulators of the GABAa receptor. It is well known that some pregnane steroids can rapidly alter CNS excitability via nongenomic mechanisms. The term neuroactive steroid has been coined to describe these compounds that can be synthesized in the brain from cholesterol. Neuroactive steroids have been shown to allosterically modulate GABA transmission via action at a unique binging site on the GABAA receptor complex. Molecular and biochemical techniques have demonstrated that the mechanism by which neuroactive steroids affect GABAergic transmission differs from that of both benzodiazepines and barbiturates. Positive modulators of GABAa receptor function, such as the 3a-hydroxylated pregnane steroid 3a-hydroxy-5P-pregnan-20-one(pregnanolone, PGN), are known to elicit a wide rage of behavioral effects including anticonvulsant, anxiolytic, and sedative/hypnotic actions.Although peripheral endocrine glands are an important endogenous source, the brain can synthesize "neurosteroids", and these have the potential to influence the activity of the GABAa receptor in the CNS. Systemic administration of steroids has clear behavioural effects.We choose PGN as our research object. The aim of the present work was to examine the central possible mechanisms underlying the effect of the neuroactive steroid PGN on the spontaneous discharge rate of rat neuron in vitro. Mainly ,we observed immediate effect of PGN in neurons and therelation between GABA and PGN, the GABA receptor antagonist bicucullin (Bic) and PGN.The majority of fast inhibitory synaptic transmission in the mammalian brain is mediated by the small amino acid GABA. By triggering the opening of postsynaptic Cl" selective ion channels of the GABAa receptor subtype, GABA increases the neuronal membrane conductance and effectively shunts the influence of excitatory neuro-transmitters. As one of the neuro-active steroids, PGN is one kind of endogenetic hormone, we attention its fast CNS effects. Pregnanolone has been found to be secreted at different body tissues as well as the CNS. It is also been reported that the neuro-steroids exert many functions such ad ease pain , anti-anxiety and anti-stress actions, in addition they can show effect in learning and memory, et al. Researchers also found the combine site of PGN may be located in GABAa receptor. After PGN combined with the PGN-site, the function of GABAa receptor changed. It is known that the GABAA receptor distributing abroad in CNS as well as SCN neurons. These are the theoretics basis of our research in PGN.In our previous study in our department, we found that when the rats fall under stress, the content of PGN in blood and brain increased. Pregnanolone can restrain the stress response and play an inhibitory role in the process of stress-induced hypertension in rats by anti-stress actions. Pregnanolone also act as a new kind of vena-anaesthesia drug. We found that after PGN was intraperitoneally injected (i.p), the decreased. We examined the neurons spontaneous discharge in brain slice. The result shows that when bath apply the PGN the spontaneous discharge rate in Hb in vitro will decrease and get back to the base line of firing rate within 10 minutes.