Effect And Mechanism Of Pregnenolone Sulfate On The Release Of Presynaptic Glutamate In Rat Nucleus Accumbens

Pregnenolone sulfate(PS) is among the most abundant and the most active members of neurosteroids.And it is possible to be a new and important signal molecule of brain.A number of studies indicated that the effect of PS on presynaptic glutamate release may have some extent of selectivity.It was effective in prelimbic cortex and hippocampus which are envolved in leaning and memory while it had no effect in movement-related region---striatum.However,the effects of pregnenlone sulfate on other parts of brain have less been studied previously.In the present study, we extend the observation to nucleus accumbes which is thought to be important in drug addiction.We investigated the effect and mechanism of PS on the miniature excitatory postsynaptic currents(mEPSCs) using whole-cell patch-clamped recording technique in slices.The results showed that PS had an obvious increasing effect on the frequency of mEPSCs in nucleus accumbens and the effect was dose-dependent.To study the mechanism of the increasing effect of PS on the frequency of mEPSCs,we investigated the influence of different antagonists on the increasing effect of PS.We found thatσ₁receptor antagonist,α₁receptor antagonist,calcium channel antagnist and PKA antagonist had no effect,while D2 receptor antagonist and PKC antagonist could completely block the effect of PS repectively.We also invested the effect of D2 receptor agonist and PKC agonist on the frequency of mEPSCs.Both of them showed an increasing effect.The enhancing effect of PS on PKC activity was futher proved by biochemecial method.Then we invested the effect of PKC antagnist on the increasing effect of D2 receptor agonist and found that PKC antagnist could block the effect of D2 receptot agonist.These results show that the effect of PS is through the activation of D2 receptor and PKC.