Serotonin potentiates the response of neurons of the superficial laminae of the rat spinal dorsal horn to γ-aminobutyric acid

Abstract Employing the Nystatin-perforated whole-cell patch-clamp recording technique, the modulatory effects of serotonin (5-HT) on γ-aminobutyric acid (GABA)-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae (laminae I and II) of the rat spinal dorsal horn. The results showed: (1) GABA acted on GABA A receptors and elicited inward Cl − currents ( I GABA ) at a holding potential (V H ) of −40 mV; (2) 5-HT potentiated GABA-induced Cl − current without affecting the reversal potential of I GABA and the apparent affinity of GABA to its receptor; (3) α-methyl-5-HT, a selective agonist of 5-HT 2 receptor, mimicked the potentiation effect of 5-HT on I GABA , whereas ketanserine, an antagonist of 5-HT 2 receptor, blocked the potentiation effect of 5-HT; (4) Chelerythrine, an inhibitor of protein kinase C, reduced the potentiation effect of 5-HT on I GABA . The present results indicate: (1) The potentiation of 5-HT on I GABA is mediated by 5-HT 2 receptor and through a protein kinase-dependent transduction pathway; (2) The interactions between 5-HT and GABA might play an important role in the modulation of nociceptive information transmission at spinal cord level.