Original Article

Acta Pharmacologica Sinica (2007) 28, 627–633; doi:10.1111/j.1745-7254.2007.00547.x

Neuropharmacology

l-Stepholidine increases the frequency of sEPSC via the activation of D1 dopamine signaling pathway in rat prelimbic cortical neurons

Project supported by the Ministry of Science and Technology (No 973-2003CB5154000 and the National Natural Science Foundation of China (No 30271495, 30230130).

Ming Gao, Chang-liang Liu, Shen Yang, Xue-chu Zhen and Guo-zhang Jin

Department of Pharmacology, State Key Laboratory of Drug Research, Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

Correspondence: Prof Guo-zhang Jin, Fax: 86-21-5492-0568. E-mail: gzjin@mail.shcnc.ac.cn

Received 12 October 2006; Accepted 8 November 2006.

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Abstract

Aim:

 

To investigate the effect of l-stepholidine (SPD) on the frequency of spontaneous excitatory postsynaptic currents (sEPSC) in the pyramidal cells between layers V and VI in the prelimbic cortex (PL).

Methods:

 

A whole-cell patch clamp in rat brain slices was used.

Results:

 

SPD significantly increased the frequency of sEPSC in a concentration-dependent manner. A selective D1 dopamine receptor antagonist SCH23390 blocked SPD-mediated effects, whereas the D1 agonist SKF38393, but not the D2/3 antagonist sulpiride, mimicked SPD-mediated increase in the frequency of sEPSC. Moreover, both protein kinase A (PKA) inhibitor N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide hydrochloride and protein kinase C (PKC) inhibitor chelerythrine attenuated the effect of SPD on sEPSC.

Conclusion:

 

SPD elicits its effect on the frequency of sEPSC on the PL pyramidal cells via presynaptic D1 receptors, and is dependent on PKA and PKC signaling pathways.

Keywords:

l-stepholidine, prelimbic cortex, whole-cell patch clamp, spontaneous excitatory postsynaptic currents, dopamine receptor

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