Expression of antinociception in response to a signal for shock is blocked after selective downregulation of mu-opioid receptors in the rostral ventromedial medulla. Brain Res Mol Brain Res 2000 Mar 29;76(2):282-8
Date
04/14/2000Pubmed ID
10762703DOI
10.1016/s0169-328x(00)00009-7Scopus ID
2-s2.0-0034728681 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Prior work has shown that release of endogenous ligands for mu-opioid receptors in the rostral ventromedial medulla (RVM) is critical for the modulation of spinal nociceptive reflexes observed during stress. In the present study, we used antisense oligodeoxynucleotides (AS ODN) to suppress synthesis of mu-opioid receptors in the RVM prior to activating descending antinociceptive systems with a signal for foot shock. Five groups of rats with RVM cannulae were trained with paired or unpaired exposures to white noise (WN) and foot shock. Over several days, they received RVM infusions of an AS ODN probe targeting exon 1 of the cloned MOR-1 receptor, an inactive missense (MS) ODN with the same base composition in which the sequence for four bases was changed, an AS ODN probe targeting exon 4, or saline. Tail-flick latencies (TFLs) were measured before, during, and after presentation of the auditory signal for shock. Rats given paired training and saline injections displayed longer TFLs than saline control rats given unpaired exposures to WN and shock, confirming the ability of the conditional stimuli (CS) to elicit antinociception. Expression of this conditional hypoalgesia (CHA) was attenuated by pretreatment with the AS ODN probe targeting exon 1, but was unaffected by pretreatment with AS ODN probe targeting exon 4 or MS ODN sequence for exon 1. However, pretreatment with the AS ODN probe targeting exon 1 did not affect expression of conditional freezing to other shock-associated cues. Testing of the same animals several days after the ODN injections showed that the attenuating effect on expression of CHA were reversible. These results support the idea that mu-opioid receptors in the RVM are critically involved in mediating expression of hypoalgesia following stress. They also provide further evidence for dissociation in the mechanisms mediating expression of aversive conditional responses.
Author List
Foo H, Helmstetter FJAuthor
Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
Acoustic StimulationAnimals
Down-Regulation
Electroshock
Exons
Fear
Male
Medulla Oblongata
Mutation, Missense
Noise
Oligonucleotide Probes
Pain
Rats
Rats, Long-Evans
Receptors, Opioid, mu
Restraint, Physical
