Morphine tolerance and naloxone receptor binding. |
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Authors: | J Harris D T Kazmierowski |
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Institution: | Division of Neurobiology, Barrow Neurological Institute of St. Joseph''s Hospital & Medical Center, Phoenix, Arizona 85013, USA |
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Abstract: | 3H-naloxone specific binding studies have confirmed the induction of receptor expansion after an acute injection of morphine, as reported by Pert et al (3) as well as the lack of expansion in chronically morphinized rats shown by Klee and Streaty (4) using dihydromorphine. With a challenging test dose of morphine given to rats maintained drug free after acute and chronic regimens of morphine, the lack of expansion as measured by 3H-naloxone specific binding persisted up to at least 4 weeks. Between 4–8 weeks receptor expansion can be re-induced with a challenging test dose. This “physical binding tolerance” is dose related. That this persistant “tolerance” is not attributable to the presence of dissociable morphine remaining after the drug regimen or challenge dose can be shown by detergent extraction and exhaustive dialysis of the standard buffer homogenate preparation as well as with fresh excised tissue. |
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