Effects of antidepressants on P2X7 receptors

Antidepressants including paroxetine, fluoxetine and desipramine are commonly used for treating depression. P2×7 receptors are member of the P2X family. Recent studies indicate that these receptors may constitute a novel potential target for the treatment of depression. In the present study, we examined the action of these antidepressants on cloned rat P2×7 receptors that were stably expressed in human embryonic kidney (HEK) 293 cells by using the whole-cell patch-clamp technique, and found that paroxetine at a dose of 10 µM could significantly reduce the inward currents evoked by the P2×7 receptors agonist BzATP by pre-incubation for 6-12 but not by acute application (10 µM) or pre-incubation for 2-6 h at a dose of 1 µM, 3 µM or 10 µM paroxetine. Neither fluoxetine nor desipramine had significant effects on currents evoked by BzATP either applied acutely or by pre-incubation at various concentrations. These results suggest that the sensitivity of rat P2×7 receptors to antidepressants is different, which may represent an unknown mechanism by which these drugs exert their therapeutic effects and side effects.