Method for training operant responding and evaluating cocaine self-administration behavior in mutant mice
Method for training operant responding and evaluating cocaine self-administration behavior in mutant mice
复制标题
DOI：
10.1007/s002130051134
复制
发表时间：
1999-11-01
影响因子：
3.4
通讯作者：
Mello, NK
中科院分区：
文献类型：
--
作者：
Caine, SB;Negus, SS;Mello, NK
使用具有靶向基因突变的小鼠进行的自我给药研究可能有助于阐明药物滥用相关效应的神经生物学机制，但前提是评估对行为的各种影响。例如，突变表型可包括改变的操作性能、健康或其他特征，这些特征可使靶基因对可卡因自我施用行为的贡献的评估复杂化。此外，在突变小鼠中增加或减少的可卡因自我给药最好在一系列可卡因剂量范围内进行评估，以评估可卡因剂量效应函数的位置和形状。将这些数据与由非药物刺激物（例如食物）维持的响应的类似量值效应函数进行比较，可能会揭示突变体中可卡因的效力或有效性的改变。已采用各种方法评估小鼠的可卡因自我给药行为，包括单次给药试验和受试者间设计，其中每只小鼠仅接受一次试验（Criswell和Ridings，1983; Carney等人，1991; Kuzmin等人，1994）。还进行了更长期的受试者内研究（Deroche et al. 1997;罗查et al. 1997）。本研究的目的是开发一种方法，用于比较可卡因自我给药的剂量-效应函数与相同受试者中食物维持行为的量-效应函数，以允许鉴定在一系列条件下特异于可卡因的突变表型的特征。
The elucidation of the neurobiological mechanisms underlying the abuse-related effects of drugs may be facilitated by self-administration studies using mice with targeted genetic mutations, but only if the various influences on the behavior are assessed. For example, a mutant phenotype may include altered operant performance, health or other characteristics that can complicate assessment of the contribution of the targeted gene to cocaine self-administration behavior. In addition, increased or decreased cocaine self-administration in mutant mice is best evaluated across a range of cocaine doses to evaluate the position and shape of the cocaine dose-effect function. A comparison of such data with similar magnitude-effect functions for responding maintained by a non-drug reinforcer such as food may reveal an altered potency or effectiveness of cocaine in mutants. Various approaches have been employed to assess cocaine self-administration behavior in mice, including single dose tests and between-subject designs in which each mouse is tested only once (Criswell and Ridings 1983; Carney et al. 1991; Kuzmin et al. 1994). Longer term, within-subject studies have also been conducted (Deroche et al. 1997; Rocha et al. 1997). The objective of the present study was to develop a method for comparing dose-effect functions for cocaine self-administration with magnitude-effect functions for food-maintained behavior in the same subjects to permit identification of features of a mutant phenotype that are specific to cocaine as a reinforcer across a range of conditions.