Facilitation of 5-hydroxytryptamine3 receptor desensitization by fluoxetine.

Effect of fluoxetine on the desensitization of the inward current mediated by 5-hydroxytryptamine3 receptors in rat nodose ganglion neurons was investigated with whole cell patch-clamp recording. 5-Hydroxytryptamine3 current desensitization was best fitted in most experiments by a single exponential function and showed little dependence on membrane potential. Fluoxetine greatly facilitated the rate of 5-hydroxytryptamine3 current desensitization in a dose-dependent manner. The effect of fluoxetine was gradual, long-lasting, voltage-independent and the recovery was incomplete. The IC50 value for the decrease of the desensitization time-constant by fluoxetine was 0.171 microM and the Hill coefficient was 1.1. Fluoxetine also inhibited the peak and steady-state 5-hydroxytryptamine3 current with the latter being more sensitive to fluoxetine. The IC50 value for the effect of fluoxetine on peak current was 1.27 microM and that on steady-state current was 0.172 microM. There is a highly significant correlation between the two effects of fluoxetine on current desensitization and on current amplitudes: r-values for the correlation between the decrease in time-constant and the reduction in peak and steady-state current amplitudes were 0.82 and 0.88, respectively (P < 0.001). This action of fluoxetine on 5-hydroxytryptamine3 receptors may be involved in the behavioral effects of fluoxetine.