Abstract

Although 5-hydroxytryptamine (5-HT) is known to be involved in the mediation of antinociception from the periaqueductal gray (PAG), its mode of action remains obscure. This investigation uses selective 5-HT(1A) receptor agonist and antagonist drugs in both behavioral and electrophysiological studies on antinociceptive mechanisms of the PAG of rats. Intraspinal administration of 8-hydroxy-dipropylaminotetralin hydrobromide (8-OH-DPAT), a selective 5-HT(1A) agonist, by microdialysis produced a dose-dependent antinociception in the radiant-heat paw withdrawal test. Dorsal horn neuronal activity was recorded extracellularly to test responses to noxious cutaneous stimuli when 8-OH-DPAT was administered iontophoretically, and it was observed that the noxious-evoked responses were inhibited in a current-related manner in all cells examined. The inhibitory effects elicited by 8-OH-DPAT could be selectively blocked by perfusion of the spinal cord with S-(--)-propranolol, a selective 5-HT(1A) antagonist. The antinociception produced by microinjection of morphine into the PAG was significantly attenuated in a dose-related manner by S-(--)-propranolol administered into the spinal cord. Similarly, the inhibition of dorsal horn neuronal responses to cutaneous mechanical stimuli produced by electrical stimulation in the PAG was reduced by S-(--)-propranolol administered into the spinal cord in the majority of cells tested. These data suggest that the release of 5-HT in the dorsal horn by stimulation in the PAG may act directly on spinal 5-HT(1A) receptors, resulting in inhibition of dorsal horn neurons. This is presumably one of the antinociceptive mechanisms of the descending serotonergic inhibitory pathway.