Neuroactive steroid pregnenolone sulphate inhibits long-term potentiation via activation of alpha2-adrenoreceptors at excitatory synapses in rat medial prefrontal cortex.
Pregnenolone sulphate (PREGS) is one of the most important neuroactive steroids. Previous study showed that PREGS enhanced long-term potentiation (LTP) via activation of post-synaptic NMDA receptors at excitatory synapses in the hippocampus. The present paper studied the effect of PREGS on LTP at excitatory synapses in the pyramidal cells of layers V-VI of the medial prefrontal cortex (mPFC) using whole-cell patch-clamp in slices and made a comparison with that in the hippocampus. We also studied the mechanism of the effect of PREGS in the mPFC. We found that PREGS inhibited induction of LTP in the mPFC and had no influence on NMDA currents, which was different from its effect in the hippocampus. Moreover, the effect of PREGS on LTP in the mPFC was cancelled by alpha2-adrenoreceptor antagonist, alpha2A-adrenoreceptor antagonist, Gi protein inhibitor, adenylate cyclase inhibitor and protein kinase A inhibitor. These results suggest that PREGS inhibits LTP via activation of the alpha2-adrenoreceptor-Gi protein-adenylate cyclase-protein kinase A signalling pathway in the mPFC.
Wang
Ze-Min
ZM
State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, People's Republic of China.
Qi
Ying-Jie
YJ
Wu
Pei-Ying
PY
Zhu
Yan
Y
Dong
Yan-Lian
YL
Cheng
Zheng-Xiang
ZX
Zhu
Yan-Hua
YH
Dong
Yi
Y
Ma
Lan
L
Zheng
Ping
P
D000262:Adenylyl Cyclases / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D016202:N-Methylaspartate / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000166:cytology*; D011284:Pregnenolone / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D013569:Synapses / Q000187:drug effects*
C547770:Adra2a protein, rat; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D018341:Receptors, Adrenergic, alpha-2; C018370:pregnenolone sulfate; D016202:N-Methylaspartate; D011284:Pregnenolone; D000262:Adenylyl Cyclases