Objective:To investigate the activity of medial prefrontal cortex (mPFC) pyramidal neurons in rats and their response to 5-hydroxytryptamine-7(5-HT7) receptor stimulation. Methods:The change of the spontaneous firing of pyramidal neurons in mPFC was observed by extracellular recording in vivo. Results:In this study,we reported that systemic and local administration of 5-HT7 receptor agonist AS19 produced excitation,inhibition and no change in the firing rate of pyramidal neurons in mPFC of rats. The mean response of the pyramidal neurons to AS19 (0.08 μg/100 nl) by systemic and local administration in mPFC was excitatory. The inhibitory effect by systemic administration of AS 19 was reversed by -酌-aminobutyricacid A receptor antagonist picrotoxinin(2 mg/kg). Systemic administration of picrotoxinin excited all the neurons examined in rats. After treatment with picrotoxinin,the local administration of AS19 increased the firing rate of the neurons. Conclusion:These results indicate that the activity of mPFC pyramidal neurons is regulated through activation of 5-HT7 receptor by direct or indirect action.