A Method for Analyzing Strain Differences in Acquisition of IV Cocaine Self-administration in Mice

Abstract

The techniques currently available for studying drug self-administration in animals offer the unique opportunity to carry out micro-analysis of initial episodes of drug use which are extremely difficult to obtain for human subjects. Nonetheless, traditional self-administration techniques do not allow a cost-effective output of large sample sizes needed for genetic analysis. Additionally, the statistical techniques that allow the integration of within-subject temporal data with genetic information are scant. We therefore propose a two-stage method for analyzing strain differences in dynamic phenotypes for a high-throughput version of the self-administration procedure. On a first phenotype-refinement stage, a change-point algorithm (Gallistel et al. (2004) Proc. Natl Acad. Sci. USA 101:13124-13131) was used to separate individual drug self-administration response curves into three distinct components. In a second stage, strains differences in these indexes were assessed. This two-stage approach is illustrated with drug self-administration data and through a computer simulation.

Intravenous Drug Self-administration in Mice: Practical Considerations

“…The procedures described in this review emphasize maintaining catheters long-term and are therefore well suited to within-subjects dose-response determinations. This approach is in contrast to acute studies of the reinforcing effects of drugs, for example with tail-vein self-administration procedures and place conditioning, in which each dose must be studied in a different group of animals, requiring a very large number of research subjects (e.g., Fink-Jensen et al 2003;Vargas-Irwin et al 2006).…”

Intravenous cocaine self-administration in a panel of inbred mouse strains differing in acute locomotor sensitivity to cocaine

“…As a result, animal models have become a useful tool for studying addiction-related behaviors (Crabbe, 2016; Lynch, Nicholson, Dance, Morgan, & Foley, 2010). Animal models provide the ability to control genetic background and the environment (Crabbe, 2016; Falcone, Lee, Lerman, & Blendy, 2016; Vargas-Irwin, van den Oord, Beardsley, & Robles, 2006); both of which contribute significantly to increased risk for addiction (Robison & Nestler, 2011; Volkow & Morales, 2015).…”