5-Hydroxytryptamine 1A receptors inhibit glutamate release in rat medullary dorsal horn neurons.

We examined 5-hydroxytryptamine 1A (5-HT1A) receptor-mediated modulation of glutamatergic transmission in rat medullary dorsal horn neurons using a conventional whole-cell patch clamp technique. 5-HT reversibly and concentration dependently decreased the amplitude of glutamatergic excitatory postsynaptic currents and increased the paired-pulse ratio, indicating that 5-HT acts presynaptically to reduce glutamate release from primary afferents. The 5-HT-induced inhibition of excitatory postsynaptic currents was partially occluded by NAN-190, a 5-HT1A receptor antagonist, and mimicked by 8-OH-DPAT, a 5-HT1A receptor agonist. Our results suggest that presynaptic 5-HT1A receptors inhibit glutamate release from trigeminal primary afferents onto medullary dorsal horn neurons, and thus in addition to other 5-HT1 receptor subtypes, 5-HT1A receptors could be a potential target for treatment of pain from orofacial tissues.