Progesterone inhibition of dopamine-induced increase in frequency of spontaneous excitatory postsynaptic currents in rat prelimbic cortical neurons

• Published in: Neuropharmacology 2004-02, Vol.46 (2), p.211-222
• Main Authors: Feng, Xue-Quan, Dong, Yi, Fu, Ying-Mei, Zhu, Yan-Hua, Sun, Jian-Li, Wang, Zhi, Sun, Feng-Yan, Zheng, Ping
• Format: Article
• Language: English
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; Animals; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Dopamine; Dopamine - pharmacology; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Limbic System - drug effects; Limbic System - physiology; Neural Inhibition - drug effects; Neural Inhibition - physiology; Neurons - drug effects; Neurons - physiology; Prelimbic cortex; Progesterone; Progesterone - pharmacology; Rats; Rats, Sprague-Dawley; Spontaneous excitatory postsynaptic current; Whole-cell patch-clamp; σ 1/D1 interaction
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2003.08.002

We examined the effects of progesterone on frequency of miniature excitatory postsynaptic currents (mEPSCs) and spontaneous excitatory postsynaptic currents (sEPSCs), and dopamine-induced increase in the frequency of sEPSCs in pyramidal cells of layers V–VI of the rat prelimbic cortex using whole-cell patch-clamp techniques in slices. The results showed that progesterone 100 μM had no effects on the frequency of mEPSCs and sEPSCs, but significantly inhibited dopamine-induced increase in frequency of sEPSCs. This was in contrast to the effect of progesterone on the effect of 5-HT, which showed no changes after progesterone. When studying the mechanism of the progesterone effect, we observed that GABA A receptor antagonist and progesterone receptor antagonist did not influence the effect of progesterone; progesterone had no effects on D1 receptor agonist, protein kinase A and protein kinase C activator-induced increase in the frequency of sEPSCs. Interestingly, σ 1 receptor antagonist could inhibit the effect of dopamine and σ 1 receptor agonist had a synergistic effect on the effect of D1 receptor agonist. These results suggest that progesterone may inhibit dopamine-induced increase in frequency of sEPSCs in rat prelimbic cortical neurons via inhibition of σ 1/D1 receptor synergism because progesterone has been known to be an antagonist of σ 1 receptor.