Actions of NMDA and cholinergic receptor antagonists in the rostral ventromedial medulla upon beta-endorphin analgesia elicited from the ventrolateral periaqueductal gray.
Analgesia elicited by morphine in the ventrolateral periaqueductal gray is mediated in part by NMDA and cholinergic receptors in the rostral ventromedial medulla because selective receptor antagonists applied to the latter structure reduced morphine analgesia elicited from the former structure. Previous studies have demonstrated that morphine and beta-endorphin employ different anatomical and neurochemical pathways in exerting their supraspinal analgesic effects. The present study evaluated whether pretreatment with either competitive (AP7, 3-10 microg) or non-competitive (MK-801, 3-10 microg) NMDA antagonists, or muscarinic (scopolamine, 5 microg) or nicotinic (mecamylamine, 1 microg) cholinergic antagonists administered into the rostral ventromedial medulla altered beta-endorphin (15 microg) analgesia elicited from the ventrolateral periaqueductal gray as measured by the tail-flick and jump tests in rats. Whereas AP7 produced minimal (11%) and transient (30 min) reductions in beta-endorphin analgesia on the jump test, MK-801 produced minimal (9%) and transient (30 min) reductions in beta-endorphin analgesia on the tail-flick test. Whereas mecamylamine failed to reduce beta-endorphin analgesia on either measure, scopolamine produced small (23%) and transient (30 min) reductions in beta-endorphin analgesia on the tail-flick test. Each of these antagonists administered into the rostral ventromedial medulla at comparable or lower doses virtually eliminated morphine analgesia elicited from the ventrolateral periaqueductal gray. The opioid mediation of beta-endorphin analgesia in the ventrolateral periaqueductal gray was confirmed by its sensitivity to naltrexone (1-20 microg) pretreatment into the same structure. These data provide further evidence for dissociations between the descending neuroanatomical and neurochemical circuitry mediating the supraspinal analgesic responses induced by morphine and beta-endorphin, and indicate that the latter response is mediated by either non-cholinergic and non-NMDA synapses within the rostral ventromedial medulla, and/or by brainstem sites outside of the rostral ventromedial medulla.
Spinella
M
M
Department of Psychology, Doctoral Subprogram, Queens College, City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA.
Znamensky
V
V
Moroz
M
M
Ragnauth
A
A
Bodnar
R J
RJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D001667:Binding, Competitive; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012601:Scopolamine / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D001615:beta-Endorphin; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D012601:Scopolamine; C031231:2-amino-7-phosphonoheptanoic acid