The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice
The tendency of a psychostimulant to increase locomotion in rodents is considered to be associated with its addictive properties. Mephedrone, one of the most popular psychoactive substances used recreationally, is known to enhance locomotor activity in mice, but little is known about the potential d...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Sciendo
2023-06-01
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| Series: | Current Issues in Pharmacy and Medical Sciences |
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| Online Access: | https://doi.org/10.2478/cipms-2023-0020 |
| _version_ | 1827909767906983936 |
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| author | Bielecka-Papierz Gabriela Poleszak Ewa Szopa Aleksandra Listos Joanna Orzelska-Gorka Jolanta Jakobczuk Małgorzata Baluk Kamila Talarek Sylwia Serefko Anna |
| author_facet | Bielecka-Papierz Gabriela Poleszak Ewa Szopa Aleksandra Listos Joanna Orzelska-Gorka Jolanta Jakobczuk Małgorzata Baluk Kamila Talarek Sylwia Serefko Anna |
| author_sort | Bielecka-Papierz Gabriela |
| collection | DOAJ |
| description | The tendency of a psychostimulant to increase locomotion in rodents is considered to be associated with its addictive properties. Mephedrone, one of the most popular psychoactive substances used recreationally, is known to enhance locomotor activity in mice, but little is known about the potential development of tolerance to its central effects. In the present study, we decided to evaluate the possible involvement of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion. Experiments were performed on adult male Albino Swiss mice, and the locomotor activity was measured automatically. Our work indicated that a 5-day administration of L-NAME (25 or 50 mg/kg/day), methylene blue (5 or 10 mg/kg/day), and L-arginine hydrochloride (i.e., 250 mg/kg/day) prevented the development of tolerance to mephedrone-induced (5 mg/kg/day) hyperlocomotion, whereas treatment with L-arginine hydrochloride at a dose of 125 mg/kg/day potentiated the development of tolerance to this central effect of mephedrone. Summarizing, our data revealed that the L-arginine-NO-cGMP pathway contributes to the development of tolerance to mephedrone’s central effects since inhibition of this signalling via blocking of NOS or NO-stimulated sGC prevented the development of tolerance to mephedrone-induced hyperlocomotion. As for cGMP-regulated phosphodiesterases, most probably they are not involved in these mechanisms. |
| first_indexed | 2024-03-13T01:43:32Z |
| format | Article |
| id | doaj.art-3905ee2d6eb3460d904f860446afe171 |
| institution | Directory Open Access Journal |
| issn | 2300-6676 |
| language | English |
| last_indexed | 2024-03-13T01:43:32Z |
| publishDate | 2023-06-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Current Issues in Pharmacy and Medical Sciences |
| spelling | doaj.art-3905ee2d6eb3460d904f860446afe1712023-07-03T10:21:22ZengSciendoCurrent Issues in Pharmacy and Medical Sciences2300-66762023-06-0136211412010.2478/cipms-2023-0020The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in miceBielecka-Papierz Gabriela0Poleszak Ewa1Szopa Aleksandra2Listos Joanna3Orzelska-Gorka Jolanta4Jakobczuk Małgorzata5Baluk Kamila6Talarek Sylwia7Serefko Anna81Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Poland2Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy, Medical University of Lublin, Poland3Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, Poland4Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland5Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland5Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland5Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland5Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Poland3Department of Clinical Pharmacy and Pharmaceutical Care, Medical University of Lublin, PolandThe tendency of a psychostimulant to increase locomotion in rodents is considered to be associated with its addictive properties. Mephedrone, one of the most popular psychoactive substances used recreationally, is known to enhance locomotor activity in mice, but little is known about the potential development of tolerance to its central effects. In the present study, we decided to evaluate the possible involvement of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion. Experiments were performed on adult male Albino Swiss mice, and the locomotor activity was measured automatically. Our work indicated that a 5-day administration of L-NAME (25 or 50 mg/kg/day), methylene blue (5 or 10 mg/kg/day), and L-arginine hydrochloride (i.e., 250 mg/kg/day) prevented the development of tolerance to mephedrone-induced (5 mg/kg/day) hyperlocomotion, whereas treatment with L-arginine hydrochloride at a dose of 125 mg/kg/day potentiated the development of tolerance to this central effect of mephedrone. Summarizing, our data revealed that the L-arginine-NO-cGMP pathway contributes to the development of tolerance to mephedrone’s central effects since inhibition of this signalling via blocking of NOS or NO-stimulated sGC prevented the development of tolerance to mephedrone-induced hyperlocomotion. As for cGMP-regulated phosphodiesterases, most probably they are not involved in these mechanisms.https://doi.org/10.2478/cipms-2023-0020mephedronel-namemethylene bluel-arginine hydrochloridesildenafil citratemice |
| spellingShingle | Bielecka-Papierz Gabriela Poleszak Ewa Szopa Aleksandra Listos Joanna Orzelska-Gorka Jolanta Jakobczuk Małgorzata Baluk Kamila Talarek Sylwia Serefko Anna The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice Current Issues in Pharmacy and Medical Sciences mephedrone l-name methylene blue l-arginine hydrochloride sildenafil citrate mice |
| title | The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice |
| title_full | The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice |
| title_fullStr | The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice |
| title_full_unstemmed | The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice |
| title_short | The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice |
| title_sort | role of the l arginine no cgmp pathway in the development of tolerance to mephedrone induced hyperlocomotion in mice |
| topic | mephedrone l-name methylene blue l-arginine hydrochloride sildenafil citrate mice |
| url | https://doi.org/10.2478/cipms-2023-0020 |
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