Abstract： Aim To explore the modulation of 5-HT on GABA-activated current (IGABA) in the membrane of rat dorsal root ganglion (DRG) neurons and its mechanism. Methods Rat DRG neurons were isolated mechanically and enzymatically, on which whole-cell patch clamp recording and repatch technique for intracellular dialysis were performed. Results In the majority of neurons examined (92.0%, 69/75 ) GABA induced a concentration-dependent inward current. In neurons sensitive to GABA preapplication of 5-HT produced potentiation effect (82. 6%, 57/69) on IGABA· Preapplication of 5-HT at concentrations of 1 × 10-6, 1 × 10-5, 1 × 10-4 and 1 × 10-3mol · L-1 potentiated IGABA by (35±8)% (n=8), (47 ±11)% (n=10), (65 ±17)% (n=9) and (75 ±18)% (n=11),respectively. This effect was mimicked by α-methyl-5-HT ( 1 × 10 -6mol · L-1 ), a specific 5-HT2 receptor agonist, and reversed by cyproheptadine, a selective 5-HT2 receptor antagonist. The potentiation of IGABA by 5-HT was irrespective to whether the I5-HT presents or not in a subset of neurons. The concentration response curves for GABA before and after pretreatment with 5-HT manifested the same threshold value and similar EC50 (2. 0 × 10-5 and 1.9 × 10-5mol · L-1, respectively) , while the maximal value of IGABA for the latter was 33.6% higher than that for the former. Intracellular dialysis with GDP-β-S or H-7 abolished the potentiation of IGABA by 5-HT, while H-9 did not. Conclusion 5-HT can potentiate GABA-activated current via PKC-dependent phosphorylation of GABAA receptor following the activation of 5-HT2 receptor.