A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats

A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its... The influence of an inhibitor of cAMP-dependent protein kinase and protein kinase C, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine), on naloxone (an opioid receptor antagonist)-precipitated withdrawal signs and changes in levels of dopamine (DA) and its metabolites in morphine- or butorphanol-dependent rats was investigated. Animals were infused continuously with morphine (a μ-opioid receptor agonist) or butorphanol (a μ/δ/κ mixed opioid receptor agonist) for 3 days. Naloxone precipitated withdrawal syndrome and decreased the levels of DA in the cortex, striatum, and midbrain; 3,4-dihydroxyphenylacetic acid (DOPAC) in the cortex, striatum, limbic areas, and midbrain; and homovanilic acid (HVA) in the striatum, limbic areas, and midbrain regions. In animals rendered dependent on butorphanol, the results obtained were similar to those of morphine-dependent rats except for the changes in DOPAC levels. Concomitant infusion of H-7 and opioid blocked both the expression of withdrawal signs and the decreases in DA, DOPAC, and HVA levels in a dose-dependent manner. These results suggest that the enhancement of cAMP-dependent protein kinase and/or protein kinase C activity accompanying the increase of DA neuron activity during continuous infusion of opioids leads to an abrupt reduction in levels of DA and its metabolites precipitated by naloxone, which is intimately involved in the expression of physical dependence on opioids. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Bulletin Elsevier

A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats

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Publisher
Elsevier
Copyright
Copyright © 2000 Elsevier Science Inc.
ISSN
0361-9230
eISSN
1873-2747
DOI
10.1016/S0361-9230(00)00273-2
Publisher site
See Article on Publisher Site

Abstract

The influence of an inhibitor of cAMP-dependent protein kinase and protein kinase C, H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine), on naloxone (an opioid receptor antagonist)-precipitated withdrawal signs and changes in levels of dopamine (DA) and its metabolites in morphine- or butorphanol-dependent rats was investigated. Animals were infused continuously with morphine (a μ-opioid receptor agonist) or butorphanol (a μ/δ/κ mixed opioid receptor agonist) for 3 days. Naloxone precipitated withdrawal syndrome and decreased the levels of DA in the cortex, striatum, and midbrain; 3,4-dihydroxyphenylacetic acid (DOPAC) in the cortex, striatum, limbic areas, and midbrain; and homovanilic acid (HVA) in the striatum, limbic areas, and midbrain regions. In animals rendered dependent on butorphanol, the results obtained were similar to those of morphine-dependent rats except for the changes in DOPAC levels. Concomitant infusion of H-7 and opioid blocked both the expression of withdrawal signs and the decreases in DA, DOPAC, and HVA levels in a dose-dependent manner. These results suggest that the enhancement of cAMP-dependent protein kinase and/or protein kinase C activity accompanying the increase of DA neuron activity during continuous infusion of opioids leads to an abrupt reduction in levels of DA and its metabolites precipitated by naloxone, which is intimately involved in the expression of physical dependence on opioids.

Journal

Brain Research BulletinElsevier

Published: Jul 15, 2000

References

  • Catalepsy and stereotyped behaviour in rats treated chronically with methadone
    Ahtee, L
  • Opiate-receptor mediated changes in monoamine synthesis in rat brain
    Garcia-Sevilla, J.A; Ahtee, L; Magnusson, T; Carlsson, A
  • Ca 2+ channel blocker, diltiazem, prevents physical dependence and the enhancement of protein kinase C activity by opioid infusion in rats
    Tokuyama, S; Feng, Y.Z; Wakabayashi, H; Ho, I.K
  • Possible involvement of protein kinases in physical dependence on opioids
    Tokuyama, S; Feng, Y.Z; Wakabayashi, H; Ho, I.K
  • Inhibitory effects of diltiazem, an L-type Ca 2+ channel blocker, on naloxone-increased glutamate levels in the locus coeruleus of opioid-dependent rats
    Tokuyama, S; Ho, I.K
  • Direct evidence for a role of glutamate in the expression of the opioid withdrawal syndrome
    Tokuyama, S; Wakabayashi, H; Ho, I.K
  • Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats
    Tokuyama, S; Wakabayashi, H; Hoskins, B; Ho, I.K

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