@article {Mei1070, author = {Jianfeng Mei and Gavril W. Pasternak}, title = {ς1 Receptor Modulation of Opioid Analgesia in the Mouse}, volume = {300}, number = {3}, pages = {1070--1074}, year = {2002}, doi = {10.1124/jpet.300.3.1070}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Opioid analgesia is influenced by many factors, including the ς1 receptor system. Current studies show the importance of supraspinal mechanisms in these ς1 actions. Given supraspinally, the ς1 receptor agonist (+)pentazocine diminished systemic μ, δ, κ1, and κ3opioid analgesia in CD-1 mice. There was a trend for the κ drugs to be more sensitive to the fixed dose of (+)pentazocine, although the differences did not achieve statistical significance. In contrast to its actions supraspinally, (+)pentazocine was without effect against morphine when both were given spinally. These findings are consistent with a supraspinal site of anti-opioid action of (+)pentazocine. Down-regulating supraspinal ς1 binding sites using an antisense approach potentiated μ, δ, κ1, and κ3 analgesia in CD-1 mice. Although equally responsive to μ drugs, BALB-c mice are far less sensitive to κ analgesics than CD-1 mice. Earlier studies reported that these different responses to κ drugs between CD-1 and BALB-c were eliminated by the concurrent administration of haloperidol, a ς1 antagonist. Antisense treatment of BALB-c mice markedly enhanced the response to κ drugs, as well as morphine. This enhanced response following antisense treatment was similar to that seen with haloperidol. These observations confirm the importance of ς1 receptors as a modulatory system influencing the analgesic activity of opioid drugs. The American Society for Pharmacology and Experimental Therapeutics}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/300/3/1070}, eprint = {https://jpet.aspetjournals.org/content/300/3/1070.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }