Neurosteroid pregnenolone sulfate inhibits stimulus-evoked EPSC via presynaptic inhibition of protein kinase A in rat prelimbic cortical neurons

• Published in: Neuropharmacology 2005-09, Vol.49 (3), p.389-399
• Main Authors: Sun, Jian-Li, Dong, Yan-Lian, Fu, Ying-Mei, Zhu, Yan-Hua, Dong, Yi, Zheng, Ping
• Format: Article
• Language: English
• Subjects: Animals; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Colforsin - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Dopamine Antagonists - pharmacology; Electric Stimulation; Enzyme Inhibitors - pharmacology; Ethylmaleimide - pharmacology; Excitatory Postsynaptic Potentials - drug effects; Excitatory synaptic transmission; Glutamate release; GTP-Binding Protein alpha Subunits, Gi-Go - antagonists & inhibitors; In Vitro Techniques; Limbic System - cytology; Limbic System - drug effects; Membrane Potentials - drug effects; Neurons - drug effects; Patch-Clamp Techniques; Pregnenolone - antagonists & inhibitors; Pregnenolone - pharmacology; Pregnenolone sulfate; Prelimbic cortex; Presynaptic Terminals - drug effects; Protein kinase A; Rats; Rats, Sprague-Dawley; Receptors, AMPA - drug effects; Serotonin Antagonists - pharmacology; Whole cell patch clamp
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2005.03.022

Pregnenolone sulfate is one of the most abundantly produced neurosteroids in the brain. The present paper studies the effect of pregnenolone sulfate on excitatory synaptic transmission in the pyramidal cells of the layer V–VI of the prelimbic cortex using whole-cell patch-clamp in slices. We found that pregnenolone sulfate inhibited stimulus-evoked excitatory postsynaptic currents (EPSC); the effect of pregnenolone sulfate was significant at concentration of 1 μM and increased with an increase in concentrations; pregnenolone sulfate had no effect on the amplitude and frequency of miniature excitatory spontaneous postsynaptic currents; pregnenolone sulfate significantly enhanced the paired-pulse facilitation (PPF) and inhibited dopamine and 5-HT-evoked increase in the frequency of spontaneous excitatory postsynaptic currents; the protein kinase A inhibitor H89 and Rp-cAMPS enhanced PPF and canceled the effect of pregnenolone sulfate on PPF; pregnenolone sulfate inhibited the protein kinase A agonist forskolin-evoked increase in the frequency of spontaneous excitatory postsynaptic currents; the G i protein inhibitor N-ethylmaleimide canceled the effect of pregnenolone sulfate on PPF. These results suggest that pregnenolone sulfate inhibits stimulus-evoked EPSC via presynaptic inhibition of protein kinase A in rat prelimbic cortical neurons.