Principles of drug abuse liability assessment in laboratory animals

Research output: Contribution to journalArticle

Abstract

This paper describes the rationale for use of preclinical assessments of abuse liability in laboratory animals, and then discusses 'cross-cutting' methodological issues that apply to behavioral evaluations intended to contribute to an abuse liability evaluation package. Issues include use of: (1) positive and negative control conditions; (2) full dose-effect evaluations, (3) multiple dependent measures, (4) pharmacokinetic evaluations to guide choice of dose ranges, (5) a species for which good methodological and comparative data are available to aid interpretation of results, and (6) appropriate methods for the group or single-subject experimental design selected. The remainder of the paper describes basic methodology by which three core pieces of behavioral data required by the Food and Drug Administration for its use in the overall abuse liability analysis can be obtained preclinically. Reinforcing effects are assessed in study of drug self-administration; drug discrimination assesses degree of overlap of interoceptive stimulus effects with relevant comparison drugs; physical dependence potential is determined by assessing whether a withdrawal syndrome occurs after chronic drug administration. Background and methodological issues specific to each procedure are discussed. A key consideration for cross-cutting and specific methodological issues is that choices made enable confident interpretation of both positive and negative results.

Original languageEnglish (US)
JournalDrug and Alcohol Dependence
Volume70
Issue number3 SUPPL.
DOIs
StatePublished - Jun 5 2003

Fingerprint

Laboratory Animals
drug abuse
liability
Substance-Related Disorders
Animals
animal
drug
abuse
evaluation
Pharmaceutical Preparations
self-administration
interpretation
Self Administration
Pharmacokinetics
United States Food and Drug Administration
withdrawal
Design of experiments
stimulus
Research Design
discrimination

Keywords

  • Abuse liability
  • Drug abuse
  • Drug development
  • Drug discrimination
  • Drug reinforcement
  • Drug withdrawal
  • FDA
  • Physical dependence
  • Self-administration

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

Cite this

Principles of drug abuse liability assessment in laboratory animals. / Ator, Nancy A; Griffiths, Roland R.

In: Drug and Alcohol Dependence, Vol. 70, No. 3 SUPPL., 05.06.2003.

Research output: Contribution to journalArticle

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