EFFECTS OF ANTIDEPRESSANTS ON THE INWARD CURRENT MEDIATED BY 5-HT3 RECEPTORS IN RAT NODOSE GANGLION NEURONS

1 Effects of three different categories of antidepressants, imipramine (tricyclic), fluoxetine (selective 5-hydroxytryptamine (5-HT) uptake inhibitor), phenelzine and iproniazid (monoamine oxidase (MAO) inhibitor) on the inward current mediated by 5-HT3 receptors were investigated in rat nodose ganglion neurones. The whole-cell patch-clamp technique was used for recording the 5-HT current. 2 All the antidepressants tested inhibited the peak 5-HT current. The inhibition gradually reached a steady level and the recovery was incomplete when antidepressants were removed. IC50 values for imipramine, fluoxetine and phenelzine were 0.54 mu M, 1.3 mu M and 4.2 mu M respectively. The correspondent Hill coefficients were 0.9, 0.87 and 0.92. 3 The antidepressants examined increased the rate of 5-HT current desensitization. IC50 values for imipramine, fluoxetine and phenelzine on the decrease in desensitization time constant were 0.11 mu M, 0.18 mu M and 2.4 mu M respectively. The correspondent Hill coefficients were 0.9, 1.14 and 1.06. 4 Intracellular applications of the protein kinase inhibitor, H-7 (100 mu M), GDP-beta-S (2 mM) and the calcium chelator BAPTA (20 mM) did not affect the 5-HT current and the actions of antidepressants on 5-HT current. 5 These results suggest that the 5-HT3 receptor is an acting site for the therapeutic use of antidepressants. The present observation is also helpful in explaining the analgesic effect of antidepressants seen in pain clinics.