Effect of Rat Immunization with Antimorphine Antibodies on Morphine Sensitivity and Predisposition to Dependence Formation

Sudakov, S. K.; Rusakova, I. V.

doi:10.1007/s10517-006-0014-6

Cited by 2 publications

(2 citation statements)

References 6 publications

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“…We previously discussed the possibility of activation of the central opioid system, suppressed during the morphine abstinence syndrome, by injection of peripheral antagonist (methylnaloxone) [5]. The results of the present study indicate that under conditions of potent activation of the central antinociceptive mechanisms by morphine, methylnaloxone suppresses this activation.…”

Section: Resultssupporting

confidence: 58%

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Hypothesis on Reciprocal Interactions between the Central and Peripheral Components of the Endogenous Opioid System

Sudakov

Trigub

2008

Bull Exp Biol Med

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A hypothesis on reciprocal interactions between the central and peripheral components of the endogenous opioid system was formulated on the basis of results of our experimental studies and published data. In order to verify this hypothesis, we studied the effects of peripheral administration of loperamide (mu-opioid receptor agonist) and methylnaloxone (opioid receptor antagonist) not penetrating through the blood-brain barrier on the pain sensitivity of rats, morphine-induced analgesia, and formation of morphine analgesia tolerance. Peripheral loperamide and methylnaloxone modulated the central mechanisms of perception of painful stimuli. This fact confirmed the hypothesis on the reciprocal interactions between the central and peripheral compartments of the endogenous opioid system. Methylnaloxone exhibits an antagonistic effect on peripheral mu-opioid receptors, which probably leads to activation of the central mu-opioid receptors and to the development of analgesia. Loperamide activates peripheral, but suppresses the central mu-opioid receptors, which leads to hyperalgesia. Methylnaloxone suppresses morphine-induced analgesia under conditions of morphine activation of the central antinociceptive mechanisms. Peripheral injection of mu-opioid agonist loperamide virtually did not modify the central compartments of the opioid system under conditions of morphine treatment. Methylnaloxone and loperamide partially prevented the development of morphine analgesia tolerance. Hence, the results confirm the hypothesis about the reciprocal interactions between the central and peripheral compartments of the endogenous opioid system. The relationships between the central and peripheral compartments of the opioid system can be more intricate when its function is modulated.

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Section: Resultssupporting

confidence: 58%

“…In order to verify this hypothesis, we studied the effect of peripheral administration of µ-and δ-opioid receptor antagonists on the severity of the abstinence syndrome in morphine-dependent rats. Naloxone easily penetrating through BBB sharply stimulated the abstinence syndrome, while methylnaloxone not penetrating into the CNS inhibited it [5].…”

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confidence: 99%