Long-term potentiation (LTP) is a form of activity-dependent synaptic plasticity that is a candidate cellular mechanism for some forms of learning and memory. Although GABAergic synaptic inhibition plays a critical role in regulating of synaptic plasticity, there is still little known about the GABAergic modulation on LTP induction in chronic preparation. In the present study we examined the effect of GABA(A) agonist, diazepam (DZM), and antagonist, picrotoxin (PTX) on the induction of LTP in the somatosensory cortex of freely moving rats for a long-term period. In adult rats a bipolar stimulating and recording electrode were implanted into corpus callusom and somatosensory cortex, respectively. Two weeks after the surgery, evoked field potential responses were recorded before, during (12 days), and after (1 month) induction period of LTP by high-frequency stimulation. The LTP characteristics were compared between control, DZM and PTX groups during the time course of recording in each rat. Administration of DZM prior to train, blocked the induction of neocortical LTP, while the PTX increased the development of LTP making the highest differential levels of LTP about 12 days after the initiation of LTP induction. Our findings suggest that the augmentation of LTP by PTX can be explained by an interaction between excitatory and inhibitory pathways. Suppression of neocortical inhibitory inputs by PTX causes enhancement in LTP induction. These results suggest that GABAergic system has an important role in synaptic plasticity and long-term modification of somatosensory cortex in freely moving rat.