Expression of antinociception in response to a signal for shock is blockedafter selective downregulation of mu-opioid receptors in the rostral ventromedial medulla

Prior work has shown that release of endogenous ligands for mu-opioid recep tors in the rostral ventromedial medulla (RVM) is critical for the modulati on of spinal nociceptive reflexes observed during stress. In the present st udy, we used antisense oligodeoxynucleotides (AS ODN) to suppress synthesis of CL-opioid receptors in the RVM prior to activating descending antinocic eptive systems with a signal for foot shock. Five groups of rats with RVM c annulae 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 base s was changed, an AS ODN probe targeting exon 4, or saline. Tail-flick late ncies (TFLs) were measured before, during, and after presentation of the au ditory signal for shock. Rats given paired training and saline injections d isplayed longer TFLs than saline control rats given unpaired exposures to W N and shock, confirming the ability of the conditional stimuli (CS) to elic it antinociception. Expression of this conditional hypoalgesia (CHA) was at tenuated by pretreatment with the AS ODN probe targeting exon I, but was un affected by pretreatment with AS ODN probe targeting exon 4 or MS ODN seque nce for exon 1. However, pretreatment with the AS ODN probe targeting exon 1 did not affect expression of conditional freezing to other shock-associat ed cues. Testing of the same animals several days after the ODN injections showed that the attenuating effect on expression of CHA were reversible. Th ese results support the idea that CL-opioid receptors in the RVM are critic ally involved in mediating expression of hypoalgesia following stress. They also provide further evidence for dissociation in the mechanisms mediating expression of aversive conditional responses. (C) 2000 Elsevier Science B. V. All rights reserved.