PRECLINICAL EVALUATION OF PHARMACOTHERAPIES FOR TREATMENT OF COCAINE AND OPIOID ABUSE USING DRUG SELF-ADMINISTRATION PROCEDURES

Drug abuse is a major public health problem, and the relationship betw een intravenous drug abuse and AIDS underscores the need for more effe ctive treatment medications. Animal models of drug self-administration are useful to systematically evaluate new treatment medications and p redict clinical efficacy. This review summarizes the status of preclin ical evaluations of medications for treatment of cocaine and opiate ab use. The basic drug self-administration methodology and the rationale for experimental designs and outcome criteria are described. Studies o f the effects of dopamine or opioid receptor agonists and antagonists as well as medications used clinically for other indications on drug s elf-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-admini stration models are valuable for preclinical assessment of medication efficacy, and we recommend some strategies to further improve evaluati on procedures. The discovery of more effective medications for substan ce abuse treatment should be facilitated by recent advances in behavio ral science, pharmacology, neurobiology and medicinal chemistry.