title: A Mouse Model for Binge-Level Methamphetamine Use.
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.
authors.affiliation: Department of Biology, Minot State University Minot, ND, USA.
authors.forename: Shkelzen
authors.initials: S
authors.lastname: Shabani
authors.affiliation: Department of Biology, Minot State University Minot, ND, USA.
authors.forename: Sydney K
authors.initials: SK
authors.lastname: Houlton
authors.affiliation: Department of Biology, Minot State University Minot, ND, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hellmuth
authors.affiliation: Department of Biology, Minot State University Minot, ND, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Mojica
authors.affiliation: Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University Portland, OR, USA.
authors.forename: John R K
authors.initials: JR
authors.lastname: Mootz
authors.affiliation: Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University Portland, OR, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University Portland, OR, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Reed
authors.affiliation: Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science UniversityPortland, OR, USA; VA Portland Health Care SystemPortland, OR, USA.
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Phillips
keywords: MAHDR; MALDR; abstinence; genetic; selected line; self-administration; voluntary consumption; withdrawal