Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice
Title: Comparison of the Effect of Chronic Treatment of Mitragynine and Morphine on Antinociceptive Behaviour and cAMP-PKA RIIβ Genes Expression in Mice Background: Mitragynine is an opioid agonist similar to morphine. Chronic administration of morphine is shown to increase the expression of cAMP...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Language: | English |
| Published: |
2018
|
| Subjects: | |
| Online Access: | http://eprints.usm.my/48214/1/Dr.%20Sakinah%20Mohd%20Akhir-24%20pages.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Title: Comparison of the Effect of Chronic Treatment of Mitragynine and Morphine on
Antinociceptive Behaviour and cAMP-PKA RIIβ Genes Expression in Mice
Background: Mitragynine is an opioid agonist similar to morphine. Chronic administration of
morphine is shown to increase the expression of cAMP-PKA RIIβ responsible for the development
of tolerance. There were no previous studies done on the effect of chronic mitragynine
administration on cAMP-PKA RIIβ gene expression. Therefore, this study aims to evaluate the
development of tolerance in mice chronically treated with morphine and mitragynine, assessed by
1) antinociceptive behavior and 2) cAMP-PKA RIIβ gene expression.
Methods: A total of 39 Swiss albino mice were randomized into 3 groups, each of which received
daily subcutaneous injection of either mitragynine, morphine or placebo, in escalating dose for 9
days. The development of tolerance was assessed by 1) Antinociceptive behaviour study:
Antinociceptive response to thermal noxious stimuli was evaluated daily using hot plate test at
52⁰C (52±2⁰C), 30 minutes after drug administration, until the signs of pain (hind-paw licking,
jumping) exhibited. The antinociceptive response was quantified as a percentage of maximal
possible effect (%MPE) and reduction in mean %MPE more than 50% was used for assessment of
antinociceptive tolerance. 2) Molecular study: The cerebral tissues (thalamus, medulla, PAG)
were dissected for sampling in order to determine cAMP-PKA RIIβ gene expression using semiquantitative
PCR method.
Results: Mitragynine-treated mice did not show tolerance by day 9 when compared to placebo
(p<0.01), similar to morphine. However, at molecular level, the cAMP-PKA RIIβ gene expression
for morphine was enhanced compared to mitragynine and placebo.
Conclusion: Chronic treatment with mitragynine did not show development of tolerance on
antinociceptive behavior and cAMP-PKA RIIβ gene expression, same as placebo, whereas
morphine showed an increased in expression of cAMP-PKA RIIβ gene despite no behavioural
antinociceptive tolerance. |
|---|