Progesterone inhibition of dopamine-induced increase in frequency of spontaneous excitatory postsynaptic currents in rat prelimbic cortical neurons.
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 microM 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, sigma(1) receptor antagonist could inhibit the effect of dopamine and sigma(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 sigma(1)/D1 receptor synergism because progesterone has been known to be an antagonist of sigma(1) receptor.
Feng
Xue-Quan
XQ
State Key Laboratory of Medical Neurobiology, Medical Centre of Fudan University, Shanghai Medical College, 138 Yixueyuan Road, Shanghai 200032, PR China.
Dong
Yi
Y
Fu
Ying-Mei
YM
Zhu
Yan-Hua
YH
Sun
Jian-Li
JL
Wang
Zhi
Z
Sun
Feng-Yan
FY
Zheng
Ping
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D008032:Limbic System / Q000187:drug effects* / Q000502:physiology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011374:Progesterone; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D004298:Dopamine