<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>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.</p>
</abstract>

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.

The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice

Chair and Department of Applied and Social Pharmacy

Laboratory of Preclinical Testing, Chair and Department of Applied and Social Pharmacy

Department of Clinical Pharmacy and Pharmaceutical Care

Department of Pharmacology and Pharmacodynamics

Current Issues in Pharmacy and Medical Sciences

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The tendency of a psychostimulant to increase locomotion in rodents is considered to be associated with its addictive properties. Mephedrone, one of the most...

The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice

Published Online: Jun 30, 2023

Page range: 114 - 120

Received: Mar 30, 2023

Accepted: May 05, 2023

DOI: https://doi.org/10.2478/cipms-2023-0020

Keywords
mephedrone, L-NAME, methylene blue, L-arginine hydrochloride, sildenafil citrate, mice

© 2023 Gabriela Bielecka-Papierz et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

The role of the L-arginine-NO-cGMP pathway in the development of tolerance to mephedrone-induced hyperlocomotion in mice

Published Online: Jun 30, 2023

Page range: 114 - 120

Received: Mar 30, 2023

Accepted: May 05, 2023

DOI: https://doi.org/10.2478/cipms-2023-0020

Keywordsmephedrone, L-NAME, methylene blue, L-arginine hydrochloride, sildenafil citrate, mice

© 2023 Gabriela Bielecka-Papierz et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
mephedrone, L-NAME, methylene blue, L-arginine hydrochloride, sildenafil citrate, mice