Involvement of glutamatergic receptors in the nucleus cuneiformis in modulating morphine-induced antinociception in rats.
The nucleus cuneiformis (CnF), located just ventrolateral to the periaqueductal gray, is part of the descending pain modulatory system. Neurons in the CnF project to medullary nucleus raphe magnus (NRM), which plays an important role on pain modulation. In this study, we investigated the effect of microinjection of the non-competitive NMDA receptor antagonist MK-801, the competitive NMDA receptor antagonist AP-7, and the kainate/AMPA receptor antagonist DNQX, alone or in combination with morphine into the nucleus cuneiformis on morphine-induced analgesia to understand the role of glutamatergic receptors in the modulating activity of morphine. Antinociception was assessed with the tail-flick test. Morphine (10, 20, 40 microg in 0.5 microl saline) had an antinociceptive effect, increasing tail-flick latency in a dose-dependent manner. Microinjection of MK-801 (10 microg/0.5 microl saline) and AP7 (3 microg/0.5 microl saline) prior to morphine microinjection (10 microg/0.5 microl saline) attenuated the antinociceptive effects of morphine, whereas DNQX (0.5 microg/0.5 microl saline) showed a partial antinociceptive effect and potentiated the analgesic effect of morphine. These results indicated that the NMDA receptor partially potentiates the antinociceptive effect of morphine. Our results suggest that NMDA but not non-NMDA receptors are involved in the antinociception produced by morphine in the CnF. The non-NMDA receptors in this area may have a facilitatory effect on nociceptive transmission. The fact that morphine's effect was potentiated by NMDA receptor suggests that projection neurons within the CnF are under tonic, glutamatergic input and when the influence of this input is blocked, the descending inhibitory system is inactivated.
Haghparast
Abbas
A
Department of Physiology and Pharmacology, School of Medicine and Neuroscience Research Center, Kerman University of Medical Sciences, P.O. Box 444, Kerman, Iran. Haghparast@yahoo.com
Gheitasi
Izad-Panah
IP
Lashgari
Reza
R
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013681:Tegmentum Mesencephali / Q000187:drug effects* / Q000502:physiology
D015763:2-Amino-5-phosphonovalerate; D000701:Analgesics, Opioid; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D009020:Morphine; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C056723:FG 9041; C031231:2-amino-7-phosphonoheptanoic acid