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...
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| Format: | Thesis |
| Language: | English |
| Published: |
2018
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| Subjects: | |
| Online Access: | http://eprints.usm.my/48214/ http://eprints.usm.my/48214/1/Dr.%20Sakinah%20Mohd%20Akhir-24%20pages.pdf |
| _version_ | 1848881092607606784 |
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| author | Akhir, Sakinah Mohd |
| author_facet | Akhir, Sakinah Mohd |
| author_sort | Akhir, Sakinah Mohd |
| building | USM Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-15T18:13:31Z |
| format | Thesis |
| id | usm-48214 |
| institution | Universiti Sains Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-15T18:13:31Z |
| publishDate | 2018 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | usm-482142021-01-31T04:29:04Z http://eprints.usm.my/48214/ Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice Akhir, Sakinah Mohd R Medicine 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. 2018 Thesis NonPeerReviewed application/pdf en http://eprints.usm.my/48214/1/Dr.%20Sakinah%20Mohd%20Akhir-24%20pages.pdf 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. |
| spellingShingle | R Medicine Akhir, Sakinah Mohd 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 |
| title_full | Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice |
| title_fullStr | Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice |
| title_full_unstemmed | Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice |
| title_short | Comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and cAMP-PKA RIIβ genes expression in mice |
| title_sort | comparison of the effect of chronic treatment of mitragynine and morphine on antinociceptive behaviour and camp-pka riiβ genes expression in mice |
| topic | R Medicine |
| url | http://eprints.usm.my/48214/ http://eprints.usm.my/48214/1/Dr.%20Sakinah%20Mohd%20Akhir-24%20pages.pdf |