Preclinical Evaluation of Pharmacotherapies for Treatment of Cocaine and Opioid Abuse Using Drug Self-Administration Procedures

摘要

Drug abuse is a major public health problem, and the relationship between intravenous drug abuse and AIDS underscores the need for more effective treatment medications. Animal models of drug self-administration are useful to systematically evaluate new treatment medications and predict clinical efficacy. This review summarizes the status of preclinical evaluations of medications for treatment of cocaine and opiate abuse. The basic drug self-administration methodology and the rationale for experimental designs and outcome criteria are described. Studies of the effects of dopamine or opioid receptor agonists and antagonists as well as medications used clinically for other indications on drug self-administration are critically examined. Where possible, the degree of concordance between clinical and preclinical studies of drug abuse treatment medications is discussed. We conclude that drug self-administration models are valuable for preclinical assessment of medication efficacy, and we recommend some strategies to further improve evaluation procedures. The discovery of more effective medications for substance abuse treatment should be facilitated by recent advances in behavioral science, pharmacology, neurobiology and medicinal chemistry.