Closed-loop stimulation is one of the important development directions of deep brain stimulation (DBS) that is promising for treating various brain disorders. Contrast to the conventional open-loop stimulation with continuous stimulation for long periods of time, the closed-loop stimulation usually utilizes short sequences of high-frequency pulses. However, neuronal responses to the high-frequency stimuli may change substantially in a short period of time because of the transient process at the beginning of stimulation. The change may affect the stimulation efficacy. To investigate the transient process of high-frequency stimuli, antidromic high-frequency stimulation (A-HFS) with different constant pulse frequencies as well as varying frequency was applied at the alveus of rat hippocampal CA1 region. The amplitude of antidromically-evoked population spike (APS) was used as an index to evaluate the neuronal responses to A-HFS. The results show that at the initial period of A-HFS with a constant pulse frequency of 100, 133 and 200 Hz, the APS decreased rapidly. A higher pulse frequency generated a faster attenuation of the APS. The mean amplitudes of APS decreased by more than half within less than 1 s. The mean half-value time of APS amplitude was ~0.96 s with 100 Hz A-HFS and decreased to ~0.21 s with the pulse frequency doubled to 200 Hz. With randomly-varying frequencies in the range of 100-200 Hz to tune the pulse interval in real time, the attenuation speed of neuronal responses was significantly slowed down to prolong the maintenance of the stimulation effect. These results provide clues to develop new DBS paradigms for the implementation of short closed-loop stimulations.