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J Pharmacol Exp Ther. 2002 Mar;300(3):1070-4.

Sigma1 receptor modulation of opioid analgesia in the mouse.

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The Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, Program in Neurosciences, Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA.


Opioid analgesia is influenced by many factors, including the sigma1 receptor system. Current studies show the importance of supraspinal mechanisms in these sigma1actions. Given supraspinally, the sigma1receptor agonist (+)pentazocine diminished systemic mu, delta, kappa1, and kappa3 opioid analgesia in CD-1 mice. There was a trend for the kappa 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 sigma1binding sites using an antisense approach potentiated mu, delta, kappa1, and kappa3 analgesia in CD-1 mice. Although equally responsive to mu drugs, BALB-c mice are far less sensitive to kappa analgesics than CD-1 mice. Earlier studies reported that these different responses to kappa drugs between CD-1 and BALB-c were eliminated by the concurrent administration of haloperidol, a sigma1 antagonist. Antisense treatment of BALB-c mice markedly enhanced the response to kappa drugs, as well as morphine. This enhanced response following antisense treatment was similar to that seen with haloperidol. These observations confirm the importance of sigma1 receptors as a modulatory system influencing the analgesic activity of opioid drugs.

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