Abstract
In this study, we characterized the role of delta-1 anddelta-2 opioid receptors in the ventromedial medulla (VMM) in the modulation of thermal nociception. Male Sprague-Dawley rats were prepared with an intracerebral guide cannula aimed at the nucleus raphe magnus or nucleus reticularis gigantocellularis pars α. Microinjection of the delta-1 opioid receptor agonist [d-Pen2,d-Pen5]enkephalin (DPDPE) or the delta-2 opioid receptor agonist [d-Ala2,Glu4]deltorphin (DELT) in the VMM increased response latency in the radiant heat tail-flick test with respective ED50 values (95% CL) of 0.66 (0.07–1.5) nmol and 0.1 (0.03–0.21) nmol. In the 55°C hot-plate test, DELT produced a modest, transient increase in response latency and DPDPE was ineffective. The antinociception produced by DPDPE was antagonized by microinjection at the same site of 1.5 pmol of thedelta-1 opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) but not by 0.15 nmol of thedelta-2 opioid receptor antagonist naltriben (NTB). Conversely, the antinociception produced by DELT was antagonized by microinjection at the same site of 0.15 nmol of NTB but not by 1.5 pmol of BNTX. These doses of BNTX or NTB alone did not alter either tail-flick or hot-plate latency when microinjected in the VMM. However, at 10-fold higher doses, BNTX lost its selectivity for thedelta-1 opioid receptor, and NTB by itself increased tail-flick and hot-plate latencies. These results collectively implicate both delta-1 and delta-2 opioid receptors in the VMM in the modulation of nociception. They also indicate that the antinociceptive effects of DPDPE and DELT can be distinguished by BNTX and NTB, providing additional support for the existence of delta-1 and delta-2 opioid receptor subtypes at supraspinal loci. Finally, the failure of effective doses of either BNTX or NTB to alter nociceptive threshold suggests that neurons in the VMM do not receive a tonic, inhibitory enkephalinergic input mediated by delta-1 ordelta-2 receptors.
Footnotes
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Send reprint requests to: Donna L. Hammond, Ph.D., Department of Anesthesia and Critical Care, The University of Chicago, 5841 South Maryland Avenue M/C 4028, Chicago, IL 60637. E-mail:dh15{at}midway.uchicago.edu
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↵1 This work was supported by United States Public Health Service Grant DA06736 (D.L.H.).
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↵2 H. L. Fields, personal communication.
- Abbreviations:
- VMM
- ventromedial medulla
- NRM
- nucleus raphe magnus
- NGCpα
- nucleus reticularis gigantocellularis pars α
- DPDPE
- [d-Pen2,d-Pen5]enkephalin
- DELT
- [d-Ala2Glu4]deltorphin
- BNTX
- 7-benzylidenenaltrexone
- NTB
- naltriben
- CL
- confidence limits
- GABA
- γ-aminobutyric acid
- HBC
- 2-hydroxypropyl-β-cyclodextrin
- Received May 29, 1997.
- Accepted August 25, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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