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Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders

Serotonin 1B receptor (5-HT(1B)R) agonists enhance cocaine intake in rats during daily self-administration but attenuate cocaine intake after prolonged abstinence. Here we investigated whether the less selective but clinically available 5-HT(1D/1B)R agonist, zolmitriptan, produces similar effects. M...

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Autores principales: Garcia, Raul, Le, Tien, Scott, Samantha N., Charmchi, Delaram, Sprout, Jamie M.L., Pentkowski, Nathan S., Neisewander, Janet L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398918/
https://www.ncbi.nlm.nih.gov/pubmed/32747623
http://dx.doi.org/10.1038/s41398-020-00956-6
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author Garcia, Raul
Le, Tien
Scott, Samantha N.
Charmchi, Delaram
Sprout, Jamie M.L.
Pentkowski, Nathan S.
Neisewander, Janet L.
author_facet Garcia, Raul
Le, Tien
Scott, Samantha N.
Charmchi, Delaram
Sprout, Jamie M.L.
Pentkowski, Nathan S.
Neisewander, Janet L.
author_sort Garcia, Raul
collection PubMed
description Serotonin 1B receptor (5-HT(1B)R) agonists enhance cocaine intake in rats during daily self-administration but attenuate cocaine intake after prolonged abstinence. Here we investigated whether the less selective but clinically available 5-HT(1D/1B)R agonist, zolmitriptan, produces similar effects. Male and free-cycling female Sprague-Dawley rats were trained to lever press for cocaine (0.75 mg/kg, i.v.) or sucrose (45 mg pellet) reinforcement until performance rates stabilized. Rats then received zolmitriptan (3.0, 5.6, and 10 mg/kg, s.c.) prior to testing for its effects on response and reinforcement rates. Under cocaine testing conditions, rats had access to the training dose for the first hour followed by a lower cocaine dose (0.075 mg/kg, i.v.) for the second hour. Zolmitriptan decreased cocaine intake at both cocaine doses and in both sexes even without a period of abstinence and without altering sucrose intake. A separate group of rats underwent identical training procedures and were tested for effects of the selective 5-HT(1B) and 5-HT(1D) receptor antagonists, SB224289 (3.2, 5.6, and 10 mg/kg, s.c.) and BRL15572 (0.3, 1.0, and 3.0 mg/kg, i.p.), respectively, alone or in combination with zolmitriptan (5.6 mg/kg, s.c.) under identical cocaine testing procedures as above. The zolmitriptan-induced decrease in cocaine intake was reversed by SB224289 and to a lesser extent by BRL15572, suggesting that the effects of zolmitriptan involve both 5-HT(1B) and 5-HT(1D) receptors. Neither zolmitriptan, SB224289, or BRL15572 altered locomotor activity at the doses effective for modulating cocaine intake. These findings suggest that zolmitriptan has potential for repurposing as a treatment for cocaine use disorders.
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spelling pubmed-73989182020-08-13 Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders Garcia, Raul Le, Tien Scott, Samantha N. Charmchi, Delaram Sprout, Jamie M.L. Pentkowski, Nathan S. Neisewander, Janet L. Transl Psychiatry Article Serotonin 1B receptor (5-HT(1B)R) agonists enhance cocaine intake in rats during daily self-administration but attenuate cocaine intake after prolonged abstinence. Here we investigated whether the less selective but clinically available 5-HT(1D/1B)R agonist, zolmitriptan, produces similar effects. Male and free-cycling female Sprague-Dawley rats were trained to lever press for cocaine (0.75 mg/kg, i.v.) or sucrose (45 mg pellet) reinforcement until performance rates stabilized. Rats then received zolmitriptan (3.0, 5.6, and 10 mg/kg, s.c.) prior to testing for its effects on response and reinforcement rates. Under cocaine testing conditions, rats had access to the training dose for the first hour followed by a lower cocaine dose (0.075 mg/kg, i.v.) for the second hour. Zolmitriptan decreased cocaine intake at both cocaine doses and in both sexes even without a period of abstinence and without altering sucrose intake. A separate group of rats underwent identical training procedures and were tested for effects of the selective 5-HT(1B) and 5-HT(1D) receptor antagonists, SB224289 (3.2, 5.6, and 10 mg/kg, s.c.) and BRL15572 (0.3, 1.0, and 3.0 mg/kg, i.p.), respectively, alone or in combination with zolmitriptan (5.6 mg/kg, s.c.) under identical cocaine testing procedures as above. The zolmitriptan-induced decrease in cocaine intake was reversed by SB224289 and to a lesser extent by BRL15572, suggesting that the effects of zolmitriptan involve both 5-HT(1B) and 5-HT(1D) receptors. Neither zolmitriptan, SB224289, or BRL15572 altered locomotor activity at the doses effective for modulating cocaine intake. These findings suggest that zolmitriptan has potential for repurposing as a treatment for cocaine use disorders. Nature Publishing Group UK 2020-08-03 /pmc/articles/PMC7398918/ /pubmed/32747623 http://dx.doi.org/10.1038/s41398-020-00956-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Garcia, Raul
Le, Tien
Scott, Samantha N.
Charmchi, Delaram
Sprout, Jamie M.L.
Pentkowski, Nathan S.
Neisewander, Janet L.
Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
title Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
title_full Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
title_fullStr Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
title_full_unstemmed Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
title_short Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
title_sort preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398918/
https://www.ncbi.nlm.nih.gov/pubmed/32747623
http://dx.doi.org/10.1038/s41398-020-00956-6
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