5-HT receptor subtypes are widely expressed in primary sensory neurons, yet so far little is known about the interaction among them. This study aimed to investigate whether the activation of 5-HT2 and 5-HT1 receptors could modulate 5-HT3 receptor mediated current in rat trigeminal ganglion (TG) neurons using whole-cell patch clamp technique. The majority of TG neurons examined responded to 5-HT (10-7-10-3M) with a fast activating and rapid desensitizing inward current (77.2%, 71/92). This 5-HT activated current (I5-HT) was blocked by ICS 205-930 and mimicked by 2-methyl-5-HT, indicating that it was mediated by 5-HT3 receptor. With a-methyl-5-HT applied prior to 5-HT application, I5-HT was otentiated in a concentration-dependent manner, with the maximal modulatory effect at 10-9 M of a-methyl-5-HT. The concentration-response curve for I5-HT pretreated with amethyl-5-HT shifts upwards compared with that for I5-HT without a-methyl-5-HT pretreatment, the maximal I5-HT value having increased by (60.3