TY - JOUR T1 - ς<sub>1</sub> Receptor Modulation of Opioid Analgesia in the Mouse JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1070 LP - 1074 DO - 10.1124/jpet.300.3.1070 VL - 300 IS - 3 AU - Jianfeng Mei AU - Gavril W. Pasternak Y1 - 2002/03/01 UR - http://jpet.aspetjournals.org/content/300/3/1070.abstract N2 - 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 ER -