Akhir, Sakinah Mohd
(2018)
Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice.
Masters thesis, Universiti Sains Malaysia.
Abstract
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.
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