Serotonin and/or an excitatory amino acid in the medial medulla mediates stimulation-produced antinociception from the lateral hypothalamus in the rat.
Several lines of evidence have demonstrated a role for the lateral hypothalamus (LH) in an endogenous system of descending inhibition. Descending inhibition from the LH relies, at least in part, on a relay(s) in the midbrain and/or medulla. The medullary nucleus raphe magnus (NRM) serves as one such relay. The present study, in rats lightly anesthetized with pentobarbital, was undertaken to systematically examine the transmitter(s) in the medial medulla mediating descending inhibition of the nociceptive tail flick (TF) reflex produced by focal electrical stimulation in the LH. The microinjection of pharmacologic receptor antagonists (5 micrograms) into the NRM revealed that the glutamate receptor antagonists, gamma-D-glutamylglycine and 2-amino-5-phosphonovalerate produced the largest increases in stimulation thresholds in the LH for inhibition of the TF reflex (107.6% and 102.6%, respectively). Methysergide, a serotonin receptor antagonist, also produced a significant increase (81.5%) in the stimulation threshold in the LH for inhibition of the TF reflex. The opioid receptor antagonist, naloxone, however, was without effect, producing only a 4.0% increase in the LH stimulation threshold. These results suggest that serotonin and/or an excitatory amino acid are transmitters at the bulbar relay in the medial medulla mediating descending inhibition of the TF reflex produced by focal electrical stimulation in the LH.
Aimone
L D
LD
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Gebhart
G F
GF
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D007026:Hypothalamic Area, Lateral / Q000503:physiopathology*; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D011903:Raphe Nuclei / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D000596:Amino Acids; D011957:Receptors, Opioid; D012701:Serotonin; D009270:Naloxone; D008784:Methysergide