Dania Cheaha1, Chayaporn Reakkamnuan2, Jakkrit Nukitram3, Somsmorn Chittrakarn4, Pimpimol Phukpattaranont5, Niwat Keawpradub6, Ekkasit Kumarnsit7. 1. Department of Biology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand; Research Unit for EEG Biomarkers of Neuronal Diseases, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. 2. Department of Physiology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand; Research Unit for EEG Biomarkers of Neuronal Diseases, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. 3. Department of Biology, Faculty of Science, Khon Kaen University, Khon Kaen 40002, Thailand. 4. Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. 5. Scientific Equipment Center, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. 6. Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. 7. Department of Physiology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand; Research Unit for EEG Biomarkers of Neuronal Diseases, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. Electronic address: ekkasit.k@psu.ac.th.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil. (M. speciosa) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a plant with potential to substitute morphine in addiction treatment program. However, its action on the central nervous system is controversial. AIM OF THE STUDY: This study investigated the effects of M. speciosa alkaloid extract on naloxone-precipitated morphine withdrawal and neural signaling in the nucleus accumbens (NAc, brain reward center) of mice. MATERIALS AND METHODS: The effects of M. speciosa alkaloid extract and mitragynine, a pure major constituent, on naloxone-precipitated morphine withdrawal were examined. Male Swiss Albino (ICR) mice were rendered dependent on morphine before injection with naloxone, a nonspecific opioid antagonist, to induce morphine withdrawal symptoms. The intensity of naloxone-precipitated morphine withdrawal was assessed from jumping behavior and diarrhea induced during a period of morphine withdrawal. To test possible addictive effect of M. speciosa alkaloid extract, mice were implanted with intracranial electrode into the NAc for local field potential (LFP) recording. Following M. speciosa alkaloid extract (80mg/kg) and morphine (15mg/kg) treatment, LFP power spectra and spontaneous motor activity were analyzed in comparison to control levels. RESULTS: One-way ANOVA and multiple comparisons revealed that M. speciosa alkaloid extract (80 and 100mg/kg) significantly decreased the number of jumping behavior induced by morphine withdrawal whereas mitragynine did not. Additionally, M. speciosa alkaloid extract significantly decreased dry and wet fecal excretions induced by morphine withdrawal. LFP analysis revealed that morphine significantly decreased alpha (9.7-12Hz) and increased low gamma (30.3-44.9Hz) and high gamma (60.5-95.7Hz) powers in the NAc whereas M. speciosa alkaloid extract did not. Spontaneous motor activity was significantly increased by morphine but not M. speciosa alkaloid extract. CONCLUSIONS: Taken together, M. speciosa alkaloid extract, but not mitragynine, attenuated the severity of naloxone-precipitated morphine withdrawal symptoms. Neural signaling in the NAc and spontaneous motor activity were sensitive to morphine but not M. speciosa alkaloid extract. Therefore, treatment with the M. speciosa alkaloid extract may be useful for opiate addiction treatment program.
ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) Havil. (M. speciosa) is among the most well-known plants used in ethnic practice of Southeast Asia. It has gained increasing attention as a plant with potential to substitute morphine in addiction treatment program. However, its action on the central nervous system is controversial. AIM OF THE STUDY: This study investigated the effects of M. speciosaalkaloid extract on naloxone-precipitated morphine withdrawal and neural signaling in the nucleus accumbens (NAc, brain reward center) of mice. MATERIALS AND METHODS: The effects of M. speciosaalkaloid extract and mitragynine, a pure major constituent, on naloxone-precipitated morphine withdrawal were examined. Male Swiss Albino (ICR) mice were rendered dependent on morphine before injection with naloxone, a nonspecific opioid antagonist, to induce morphine withdrawal symptoms. The intensity of naloxone-precipitated morphine withdrawal was assessed from jumping behavior and diarrhea induced during a period of morphine withdrawal. To test possible addictive effect of M. speciosaalkaloid extract, mice were implanted with intracranial electrode into the NAc for local field potential (LFP) recording. Following M. speciosaalkaloid extract (80mg/kg) and morphine (15mg/kg) treatment, LFP power spectra and spontaneous motor activity were analyzed in comparison to control levels. RESULTS: One-way ANOVA and multiple comparisons revealed that M. speciosaalkaloid extract (80 and 100mg/kg) significantly decreased the number of jumping behavior induced by morphine withdrawal whereas mitragynine did not. Additionally, M. speciosaalkaloid extract significantly decreased dry and wet fecal excretions induced by morphine withdrawal. LFP analysis revealed that morphine significantly decreased alpha (9.7-12Hz) and increased low gamma (30.3-44.9Hz) and high gamma (60.5-95.7Hz) powers in the NAc whereas M. speciosaalkaloid extract did not. Spontaneous motor activity was significantly increased by morphine but not M. speciosaalkaloid extract. CONCLUSIONS: Taken together, M. speciosaalkaloid extract, but not mitragynine, attenuated the severity of naloxone-precipitated morphine withdrawal symptoms. Neural signaling in the NAc and spontaneous motor activity were sensitive to morphine but not M. speciosaalkaloid extract. Therefore, treatment with the M. speciosaalkaloid extract may be useful for opiate addiction treatment program.
Authors: Elisabeth Prevete; Kim Paula Colette Kuypers; Eef Lien Theunissen; Ornella Corazza; Giuseppe Bersani; Johannes Gerardus Ramaekers Journal: Hum Psychopharmacol Date: 2021-07-26 Impact factor: 2.130