Research Article: Preclinical Determinants of Drug Choice under Concurrent Schedules of Drug Self-Administration

Date Published: November 28, 2012

Publisher: Hindawi Publishing Corporation

Author(s): Matthew L. Banks, S. Stevens Negus.


Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for over 50 years. While there are numerous permutations of this procedure, this paper will specifically focus on choice procedures using concurrent schedules of intravenous drug self-administration. The aims of this paper are to first highlight the evolution of drug choice procedures and then review the subsequent preclinical body of literature utilizing these choice procedures to understand the environmental, pharmacological, and biological determinants of the reinforcing stimulus effects of drugs. A main rationale for this paper is our proposition that choice schedules are underutilized in investigating the reinforcing effects of drugs in assays of drug self-administration. Moreover, we will conclude with potential future directions and unexplored scientific space for the use of drug choice procedures.

Partial Text

Drug self-administration procedures have played a critical role in the experimental analysis of psychoactive compounds, such as cocaine, for more than 50 years. In general, preclinical drug self-administration procedures are utilized for two main scientific purposes. One purpose is in abuse liability testing of psychoactive compounds for potential scheduling as controlled substances by the Drug Enforcement Agency, and there are already excellent reviews on the use of drug self-administration procedures for this purpose, see [1, 2]. The other main purpose of drug self-administration procedures is in understanding the pharmacological, environmental and biological determinants of drug-taking behavior as a model of drug addiction. This paper will focus on the use of concurrent-choice schedules of drug self-administration to address this latter purpose.

Research on the reinforcing effects of drugs has been slow to adopt concurrent schedules of reinforcement; however, this paper has argued that choice procedures can play a useful role in preclinical research on drug reinforcement and determinants of drugs use. There are still critical gaps in our knowledge, and there remains much intellectual space to be explored. One future direction might be the establishment of drug versus nondrug alternative choice procedures involving abused drugs other than the classical compounds cocaine and heroin. The degree to which drug choice can be maintained by other novel drug class such as benzodiazepines, cannabinoids, and nicotine remains to be elucidated. Another future direction might be to examine the impact of nondrug alternative reinforcers other than food. Food is an easy alternative reinforcer to control in preclinical laboratories, but there are certainly other nondrug reinforcers (e.g., access to receptive mate or social interactions) that are available as research tools that have yet to be fully explored. As one example of a choice procedure using a nondrug alternative reinforcer other than food, one intriguing study examined effects of putative anorectic drugs on choice between food and visual access to a room containing other monkeys [95]. This type of social reinforcer has yet to be manipulated in studies of drug choice. Finally, a third potential future direction is the integration of drug reinforcers into decision-making “choice” tasks commonly used to assess cognitive function. For example, impaired delay discounting is a cognitive trait commonly linked to drug abuse [96, 97], and delay discounting is often assessed preclinically in assays that compare choice between a delayed high-magnitude reinforcer and an immediate low-magnitude reinforcer [98]. Strikingly, preclinical research with this type of assay has relied exclusively on food as the consequent stimulus. The introduction of drugs as reinforcers into delay discounting and other cognitive tasks may provide new insights into the relationship between cognitive function and drug use. Overall, the body of literature cited in this paper supports the notion that choice procedures can facilitate data interpretation by providing a rate-independent measure of drug reinforcement, improve concordance between preclinical and clinical studies in translational research, and provide experimental access to critical independent variables that influence drug choice and drug addiction in natural environments.




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