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A Mouse Model for Binge-Level Methamphetamine Use

Binge/crash cycles of methamphetamine (MA) use are frequently reported by individuals suffering from MA use disorders. A MA binge is self-reported as multiple daily doses that commonly accumulate to 800 mg/day (~10 mg/kg/day for a 170 pound human). A genetic animal model with a similar vulnerability...

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Autores principales: Shabani, Shkelzen, Houlton, Sydney K., Hellmuth, Laura, Mojica, Erika, Mootz, John R. K., Zhu, Zhen, Reed, Cheryl, Phillips, Tamara J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090006/
https://www.ncbi.nlm.nih.gov/pubmed/27853417
http://dx.doi.org/10.3389/fnins.2016.00493
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author Shabani, Shkelzen
Houlton, Sydney K.
Hellmuth, Laura
Mojica, Erika
Mootz, John R. K.
Zhu, Zhen
Reed, Cheryl
Phillips, Tamara J.
author_facet Shabani, Shkelzen
Houlton, Sydney K.
Hellmuth, Laura
Mojica, Erika
Mootz, John R. K.
Zhu, Zhen
Reed, Cheryl
Phillips, Tamara J.
author_sort Shabani, Shkelzen
collection PubMed
description Binge/crash cycles of methamphetamine (MA) use are frequently reported by individuals suffering from MA use disorders. A MA binge is self-reported as multiple daily doses that commonly accumulate to 800 mg/day (~10 mg/kg/day for a 170 pound human). A genetic animal model with a similar vulnerability to binge-level MA intake is missing. We used selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mouse lines to determine whether several procedural variations would result in binge-level MA intake. Data were also collected in two progenitor populations of the MA drinking lines, the DBA/2J (D2) strain and the F2 cross of the D2 and C57BL/6J strains. The impact of 3 factors was examined: (1) concentration of MA in the two-bottle choice procedure used for selective breeding; (2) ratio of bottles containing MA vs. water, and (3) length of the withdrawal (or abstinence) period between MA drinking sessions. When MA concentration was progressively increased every 4 days in 20 mg/l amounts from 20 to 140 mg/l, maximum intake in MALDR mice was 1.1 mg/kg, whereas MAHDR mice consumed as much as 14.6 mg/kg. When these concentrations were tested in a multiple bottle choice procedure, the highest ratio of MA to water bottles (3:1) was associated with escalated MA intake of up to 29.1 mg/kg in MAHDR mice and 12.0 mg/kg in F2 mice; MALDR mice did not show a ratio-dependent escalation in MA intake. Finally, MAHDR and D2 mice were offered 3 bottles of MA vs. water at increasing concentrations from 20 to 80 mg/l, and tested under an intermittent 6-h withdrawal period, which was lengthened to 30 h (D2 mice) or to 30 or 78 h (MAHDR). D2 and MAHDR mice initially consumed similar amounts of 14–16 mg/kg MA, but D2 mice reduced their MA intake 3-fold after introduction of 30-h abstinence periods, whereas MAHDR mice retained their high level of intake regardless of withdrawal period. MAHDR mice provide a genetic model of binge-level MA intake appropriate for the study of associated MA-induced neurobiological changes and pharmaceutical treatments.
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spelling pubmed-50900062016-11-16 A Mouse Model for Binge-Level Methamphetamine Use Shabani, Shkelzen Houlton, Sydney K. Hellmuth, Laura Mojica, Erika Mootz, John R. K. Zhu, Zhen Reed, Cheryl Phillips, Tamara J. Front Neurosci Neuroscience Binge/crash cycles of methamphetamine (MA) use are frequently reported by individuals suffering from MA use disorders. A MA binge is self-reported as multiple daily doses that commonly accumulate to 800 mg/day (~10 mg/kg/day for a 170 pound human). A genetic animal model with a similar vulnerability to binge-level MA intake is missing. We used selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mouse lines to determine whether several procedural variations would result in binge-level MA intake. Data were also collected in two progenitor populations of the MA drinking lines, the DBA/2J (D2) strain and the F2 cross of the D2 and C57BL/6J strains. The impact of 3 factors was examined: (1) concentration of MA in the two-bottle choice procedure used for selective breeding; (2) ratio of bottles containing MA vs. water, and (3) length of the withdrawal (or abstinence) period between MA drinking sessions. When MA concentration was progressively increased every 4 days in 20 mg/l amounts from 20 to 140 mg/l, maximum intake in MALDR mice was 1.1 mg/kg, whereas MAHDR mice consumed as much as 14.6 mg/kg. When these concentrations were tested in a multiple bottle choice procedure, the highest ratio of MA to water bottles (3:1) was associated with escalated MA intake of up to 29.1 mg/kg in MAHDR mice and 12.0 mg/kg in F2 mice; MALDR mice did not show a ratio-dependent escalation in MA intake. Finally, MAHDR and D2 mice were offered 3 bottles of MA vs. water at increasing concentrations from 20 to 80 mg/l, and tested under an intermittent 6-h withdrawal period, which was lengthened to 30 h (D2 mice) or to 30 or 78 h (MAHDR). D2 and MAHDR mice initially consumed similar amounts of 14–16 mg/kg MA, but D2 mice reduced their MA intake 3-fold after introduction of 30-h abstinence periods, whereas MAHDR mice retained their high level of intake regardless of withdrawal period. MAHDR mice provide a genetic model of binge-level MA intake appropriate for the study of associated MA-induced neurobiological changes and pharmaceutical treatments. Frontiers Media S.A. 2016-11-02 /pmc/articles/PMC5090006/ /pubmed/27853417 http://dx.doi.org/10.3389/fnins.2016.00493 Text en Copyright © 2016 Shabani, Houlton, Hellmuth, Mojica, Mootz, Zhu, Reed and Phillips. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shabani, Shkelzen
Houlton, Sydney K.
Hellmuth, Laura
Mojica, Erika
Mootz, John R. K.
Zhu, Zhen
Reed, Cheryl
Phillips, Tamara J.
A Mouse Model for Binge-Level Methamphetamine Use
title A Mouse Model for Binge-Level Methamphetamine Use
title_full A Mouse Model for Binge-Level Methamphetamine Use
title_fullStr A Mouse Model for Binge-Level Methamphetamine Use
title_full_unstemmed A Mouse Model for Binge-Level Methamphetamine Use
title_short A Mouse Model for Binge-Level Methamphetamine Use
title_sort mouse model for binge-level methamphetamine use
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5090006/
https://www.ncbi.nlm.nih.gov/pubmed/27853417
http://dx.doi.org/10.3389/fnins.2016.00493
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