Ca 2+ channel blocker, diltiazem, prevents physical dependence and the enhancement of protein kinase C activity by opioid infusion in rats

Ca 2+ channel blocker, diltiazem, prevents physical dependence and the enhancement of protein... The influence of an L-type Ca 2+ channel blocker, diltiazem {(2 S - cis )-3-(acetyloxy)-5-(2-(dimethylamino)-ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5 H )-one} on the behavioral signs of naloxone (opioid receptor antagonist)-precipitated withdrawal syndrome and the enhancement of protein kinase C activity in the pons/medulla regions of rats rendered dependent on morphine (μ-opioid receptor agonist) or butorphanol (μ/δ/κ mixed opioid receptor agonist) was investigated. The expression of physical dependence produced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl per h) or butorphanol (26 nmol/μl per h) for 3 days, as evaluated by naloxone (5 mg/kg, i.p.)-precipitated withdrawal signs, was dose dependently attenuated by concomitant infusion of diltiazem (10 and 100 nmol/μl per h). Furthermore, diltiazem (100 nmol/μl per h) completely inhibited the enhancement of cytosolic protein kinase C activity in the pons/medulla regions in rats rendered dependent by continuous infusion with morphine or butorphanol. These results suggest that the augmentation of intracellular Ca 2+ concentration mediated through L-type Ca 2+ channels during continuous opioid infusion leads to the enhancement of cytosolic protein kinase C activity in the pons/medulla region which is intimately involved in the development and/or expression of physical dependence on opioids. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

Ca 2+ channel blocker, diltiazem, prevents physical dependence and the enhancement of protein kinase C activity by opioid infusion in rats

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Ltd
ISSN
0014-2999
DOI
10.1016/0014-2999(95)00140-G
Publisher site
See Article on Publisher Site

Abstract

The influence of an L-type Ca 2+ channel blocker, diltiazem {(2 S - cis )-3-(acetyloxy)-5-(2-(dimethylamino)-ethyl)-2,3-dihydro-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5 H )-one} on the behavioral signs of naloxone (opioid receptor antagonist)-precipitated withdrawal syndrome and the enhancement of protein kinase C activity in the pons/medulla regions of rats rendered dependent on morphine (μ-opioid receptor agonist) or butorphanol (μ/δ/κ mixed opioid receptor agonist) was investigated. The expression of physical dependence produced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/μl per h) or butorphanol (26 nmol/μl per h) for 3 days, as evaluated by naloxone (5 mg/kg, i.p.)-precipitated withdrawal signs, was dose dependently attenuated by concomitant infusion of diltiazem (10 and 100 nmol/μl per h). Furthermore, diltiazem (100 nmol/μl per h) completely inhibited the enhancement of cytosolic protein kinase C activity in the pons/medulla regions in rats rendered dependent by continuous infusion with morphine or butorphanol. These results suggest that the augmentation of intracellular Ca 2+ concentration mediated through L-type Ca 2+ channels during continuous opioid infusion leads to the enhancement of cytosolic protein kinase C activity in the pons/medulla region which is intimately involved in the development and/or expression of physical dependence on opioids.

Journal

European Journal of PharmacologyElsevier

Published: Jun 6, 1995

References

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