Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice
Emergence of analgesic tolerance and dependence to morphine is frequently the limiting factor in the use of this agent in the management of pain. Hence, this study aimed to investigate the beneficial effects of the natural compound carveol (CV) against morphine antinociceptive tolerance, dependence...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
|
| Series: | Heliyon |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024038404 |
| _version_ | 1797224219369537536 |
|---|---|
| author | Ismail Badshah Neelum Gul Qazi Maira Anwar Bushra Shaukat Muhammad Imran Khan Babar Murtaza |
| author_facet | Ismail Badshah Neelum Gul Qazi Maira Anwar Bushra Shaukat Muhammad Imran Khan Babar Murtaza |
| author_sort | Ismail Badshah |
| collection | DOAJ |
| description | Emergence of analgesic tolerance and dependence to morphine is frequently the limiting factor in the use of this agent in the management of pain. Hence, this study aimed to investigate the beneficial effects of the natural compound carveol (CV) against morphine antinociceptive tolerance, dependence and conditioned place preference (CPP) in mice. Behavioural paradigms included hot plate and tail-flick (for tolerance), observation of withdrawal signs (for dependence) while biochemical tests involved the assays for mRNA expression, nitrite levels, antioxidants, and immunohistochemistry studies. Behavioural tests indicated that treatment with CV significantly attenuated the morphine analgesic tolerance, physical dependence and CPP in mice. It was observed during biochemical analysis that CV-treated animals exhibited reduced mRNA expression of inducible nitric oxide synthase (iNOS) and NR2B (an NMDA subtype). In addition, decreased levels of nitrite were observed in mouse hippocampus following CV treatment than morphine administration only. Further, CV enhanced the neuronal innate antioxidants including Glutathione-S-Transferase (GST), glutathione (GSH) and catalase (CAT), while curtailed lipid peroxidase (LPO) levels in mice brain tissues. Moreover, CV exerted significant anti-inflammatory effects as evidenced by reduced expression of TNF-α and p–NF–κB in these animals than with morphine treatment only. Together, anti-inflammatory and antioxidant effects might confer needed neuro-protection following morphine administration. These observations warrant further investigations of the beneficial role of CV as a novel agent in overcoming the development of tolerance and physical dependence following morphine use. |
| first_indexed | 2024-04-24T13:49:38Z |
| format | Article |
| id | doaj.art-b68a65b09bee46218d6144430c5ed179 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:49:38Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-b68a65b09bee46218d6144430c5ed1792024-04-04T05:05:59ZengElsevierHeliyon2405-84402024-03-01106e27809Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in miceIsmail Badshah0Neelum Gul Qazi1Maira Anwar2Bushra Shaukat3Muhammad Imran Khan4Babar Murtaza5Riphah Institute of Pharmaceutical Sciences, Islamabad, PakistanDepartment of Pharmacy, Iqra University, Islamabad, PakistanRiphah Institute of Pharmaceutical Sciences, Islamabad, PakistanDepartment of Pharmacy, Government College University, Faisalabad, PakistanDepartment of Biomedical Sciences, Pak-Austria Fachhochschule Institute of Applied Sciences and Technology, Haripur, Pakistan; Corresponding author.Riphah Institute of Pharmaceutical Sciences, Islamabad, Pakistan; Corresponding author.Emergence of analgesic tolerance and dependence to morphine is frequently the limiting factor in the use of this agent in the management of pain. Hence, this study aimed to investigate the beneficial effects of the natural compound carveol (CV) against morphine antinociceptive tolerance, dependence and conditioned place preference (CPP) in mice. Behavioural paradigms included hot plate and tail-flick (for tolerance), observation of withdrawal signs (for dependence) while biochemical tests involved the assays for mRNA expression, nitrite levels, antioxidants, and immunohistochemistry studies. Behavioural tests indicated that treatment with CV significantly attenuated the morphine analgesic tolerance, physical dependence and CPP in mice. It was observed during biochemical analysis that CV-treated animals exhibited reduced mRNA expression of inducible nitric oxide synthase (iNOS) and NR2B (an NMDA subtype). In addition, decreased levels of nitrite were observed in mouse hippocampus following CV treatment than morphine administration only. Further, CV enhanced the neuronal innate antioxidants including Glutathione-S-Transferase (GST), glutathione (GSH) and catalase (CAT), while curtailed lipid peroxidase (LPO) levels in mice brain tissues. Moreover, CV exerted significant anti-inflammatory effects as evidenced by reduced expression of TNF-α and p–NF–κB in these animals than with morphine treatment only. Together, anti-inflammatory and antioxidant effects might confer needed neuro-protection following morphine administration. These observations warrant further investigations of the beneficial role of CV as a novel agent in overcoming the development of tolerance and physical dependence following morphine use.http://www.sciencedirect.com/science/article/pii/S2405844024038404CarveolMorphineToleranceDependenceNMDANitric oxide |
| spellingShingle | Ismail Badshah Neelum Gul Qazi Maira Anwar Bushra Shaukat Muhammad Imran Khan Babar Murtaza Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice Heliyon Carveol Morphine Tolerance Dependence NMDA Nitric oxide |
| title | Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice |
| title_full | Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice |
| title_fullStr | Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice |
| title_full_unstemmed | Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice |
| title_short | Carveol mitigates the development of the morphine anti-nociceptive tolerance, physical dependence, and conditioned place preference in mice |
| title_sort | carveol mitigates the development of the morphine anti nociceptive tolerance physical dependence and conditioned place preference in mice |
| topic | Carveol Morphine Tolerance Dependence NMDA Nitric oxide |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024038404 |
| work_keys_str_mv | AT ismailbadshah carveolmitigatesthedevelopmentofthemorphineantinociceptivetolerancephysicaldependenceandconditionedplacepreferenceinmice AT neelumgulqazi carveolmitigatesthedevelopmentofthemorphineantinociceptivetolerancephysicaldependenceandconditionedplacepreferenceinmice AT mairaanwar carveolmitigatesthedevelopmentofthemorphineantinociceptivetolerancephysicaldependenceandconditionedplacepreferenceinmice AT bushrashaukat carveolmitigatesthedevelopmentofthemorphineantinociceptivetolerancephysicaldependenceandconditionedplacepreferenceinmice AT muhammadimrankhan carveolmitigatesthedevelopmentofthemorphineantinociceptivetolerancephysicaldependenceandconditionedplacepreferenceinmice AT babarmurtaza carveolmitigatesthedevelopmentofthemorphineantinociceptivetolerancephysicaldependenceandconditionedplacepreferenceinmice |