Inhibition of mesencephalic morphine analgesia by methysergide in the medial ventral medulla of rats.
The neural substrates of endogenous supraspinal opioid pain inhibition are mediated in part by connections between the midbrain periaqueductal gray (PAG) and the ventral-medial medulla, including the nucleus raphe magnus (NRM) and nucleus reticularis gigantocellularis (NRGC). To ascertain whether a serotonergic synapse participated in this pathway, the present study determined whether microinjections of methysergide into the NRM or NRGC would alter analgesia elicited by morphine microinjections into the PAG. Morphine (2.5 micrograms) in the PAG and immediately adjacent areas produced significant analgesia on the tail-flick and jump tests in rats. Pretreatment with the serotonin receptor antagonist methysergide (0.5-5 micrograms) in either the NRM or NRGC significantly reduced morphine analgesia elicited from the PAG by 69% on the tail-flick and by 50% on the jump tests without altering basal nociceptive thresholds. Medullary placements ventral or lateral to the NRM/NRGC failed to support this antagonistic effect. These data indicate that a ventro-medial medullary serotonergic synapse participates in the transmission of opioid pain-inhibitory signals from the PAG.
Kiefel
J M
JM
Department of Psychology and Neuropsychology, Queens College, City University of New York, Flushing 11367.
Cooper
M L
ML
Bodnar
R J
RJ
D000818:Animals; D001931:Brain Mapping; D004305:Dose-Response Relationship, Drug; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008636:Mesencephalon / Q000187:drug effects*; D008784:Methysergide / Q000494:pharmacology*; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects*; D009434:Neural Pathways / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D010487:Periaqueductal Gray / Q000187:drug effects; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013376:Substantia Gelatinosa / Q000187:drug effects
D011957:Receptors, Opioid; D009020:Morphine; D008784:Methysergide