Shabani Shkelzen, Schmidt Bryan, Ghimire Bikalpa, Houlton Sydney K, Hellmuth Laura, Mojica Erika, Phillips Tamara J
Grand Valley State University, Biomedical Sciences, Allendale, Michigan, USA.
Minot State University, Department of Biology, Minot, North Dakota, USA.
Genes Brain Behav. 2019 Mar;18(3):e12533. doi: 10.1111/gbb.12533. Epub 2018 Nov 26.
Binge methamphetamine (MA) users have higher MA consumption, relapse rates and depression-like symptoms during early periods of withdrawal, compared with non-binge users. The impact of varying durations of MA abstinence on depression-like symptoms and on subsequent MA intake was examined in mice genetically prone to binge-level MA consumption. Binge-level MA intake was induced using a multiple-bottle choice procedure in which mice were offered one water drinking tube and three tubes containing increasing concentrations of MA in water, or four water tubes (control group). In two studies, depression-like symptoms were measured using a tail-suspension test and a subsequent forced-swim test, after forced abstinence of 6 and 30 hours from a 28-day course of chronic MA intake. An additional study measured the same depression-like symptoms, as well as MA intake, after prolonged abstinence of 1 and 2 weeks. MA high drinking mice and one of their progenitor strains DBA/2J escalated their MA intake with increasing MA concentration; however, MA high drinking mice consumed almost twice as much MA as DBA/2J mice. Depression-like symptoms were significantly higher early after MA access was withdrawn, compared to levels in drug-naïve controls, with more robust effects of MA withdrawal observed in MA high drinking than DBA/2J mice. When depression-like symptoms were examined after 1 or 2 weeks of forced abstinence in MA high drinking mice, depression-like symptoms dissipated, and subsequent MA intake was high. The MA high drinking genetic mouse model has strong face validity for human binge MA use and behavioral sequelae associated with abstinence.
与非暴饮暴食型甲基苯丙胺（MA）使用者相比，暴饮暴食型MA使用者在戒断早期有更高的MA消耗量、复发率和类似抑郁的症状。在基因上倾向于暴饮暴食水平MA消耗的小鼠中，研究了不同时长的MA戒断对类似抑郁症状和随后MA摄入量的影响。使用多瓶选择程序诱导小鼠达到暴饮暴食水平的MA摄入量，在此程序中，给小鼠提供一根饮水管和三根含有浓度递增的MA水溶液的管子，或者四根水管（对照组）。在两项研究中，在经过28天的慢性MA摄入后，分别强制戒断6小时和30小时，然后使用悬尾试验和随后的强迫游泳试验来测量类似抑郁的症状。另一项研究在延长戒断1周和2周后，测量了相同的类似抑郁症状以及MA摄入量。MA高饮小鼠及其祖系之一DBA/2J随着MA浓度增加而提高其MA摄入量；然而，MA高饮小鼠消耗的MA几乎是DBA/2J小鼠的两倍。与未接触过药物的对照组相比，在停止接触MA后早期，类似抑郁的症状明显更严重，在MA高饮小鼠中观察到的MA戒断效应比DBA/2J小鼠更强烈。当在MA高饮小鼠中强制戒断1周或2周后检查类似抑郁的症状时，类似抑郁的症状消失了，随后的MA摄入量很高。MA高饮基因小鼠模型对于人类暴饮暴食型MA使用以及与戒断相关的行为后遗症具有很强的表面效度。
