A mouse model for binge-level methamphetamine use

Shkelzen Shabani, Sydney K. Houlton, Laura Hellmuth, Erika Mojica, John R K Mootz, Zhen Zhu, Cheryl Reed, Tamara Phillips

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article number493
JournalFrontiers in Neuroscience
Volume10
Issue numberNOV
DOIs
StatePublished - 2016

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Methamphetamine
Drinking
Inbred DBA Mouse
Genetic Models
Water

Keywords

  • Abstinence
  • Genetic
  • MAHDR
  • MALDR
  • Selected line
  • Self-administration
  • Voluntary consumption
  • Withdrawal

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Shabani, S., Houlton, S. K., Hellmuth, L., Mojica, E., Mootz, J. R. K., Zhu, Z., ... Phillips, T. (2016). A mouse model for binge-level methamphetamine use. Frontiers in Neuroscience, 10(NOV), [493]. https://doi.org/10.3389/fnins.2016.00493

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.

In: Frontiers in Neuroscience, Vol. 10, No. NOV, 493, 2016.

Research output: Contribution to journalArticle

Shabani, S, Houlton, SK, Hellmuth, L, Mojica, E, Mootz, JRK, Zhu, Z, Reed, C & Phillips, T 2016, 'A mouse model for binge-level methamphetamine use', Frontiers in Neuroscience, vol. 10, no. NOV, 493. https://doi.org/10.3389/fnins.2016.00493
Shabani S, Houlton SK, Hellmuth L, Mojica E, Mootz JRK, Zhu Z et al. A mouse model for binge-level methamphetamine use. Frontiers in Neuroscience. 2016;10(NOV). 493. https://doi.org/10.3389/fnins.2016.00493
Shabani, Shkelzen ; Houlton, Sydney K. ; Hellmuth, Laura ; Mojica, Erika ; Mootz, John R K ; Zhu, Zhen ; Reed, Cheryl ; Phillips, Tamara. / A mouse model for binge-level methamphetamine use. In: Frontiers in Neuroscience. 2016 ; Vol. 10, No. NOV.
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