Drug-maintained behavior serves as an appropriate model to assess potential treatments for drug abuse. Recent studies have shown that agonist treatments can decrease responding maintained by cocaine, or opiates. These effects have been shown to be persistent, and without deleterious consequence. They are interpreted as a substitution effect, similar to that expected of methadone for heroin abuse and nicotine patches for tobacco abuse. Confirmation of this notion may lead to the development of agonist treatments for other forms of substance abuse. The utility of this approach is that compliance is expected to be greater than that seen with antagonist-based treatments. in addition, agonists only decrease drug-intake, while increases in drug intake have been observed with antagonists. Preliminary clinical reports suggest that agonists exhibit efficacy in humans. Nevertheless, this form of treatment deserves more study before being implemented. One reason is that other forms of treatment may be more efficacious. For example, some studies have shown that providing access to non-drug reinforcers can also decrease drug- maintained responding. Another reason is that few studies have addressed the therapeutic ratio for agonist effects, nor the range of conditions under which drug-seeking can be decreased. The current studies are designed to more fully assess the nature of agonist treatments on drug- maintained behavior. In doing so, several issues related to obtaining a better understanding of determinants of the reinforcing efficacy of drugs will be addressed. Traditional methods of determining the reinforcing effects of drugs have been limited to either the extent to which different doses will support higher ratio requirements,or the assessment of rates of responding maintained by different doses of a drug. While the former has been criticized for a lack of stability, the latter is rarely accomplished due to the large amount of data required. Recently, it has been suggested that these two indices can be combined to describe a single function relating reinforcing effects of drugs behavioral output per dose. This possibility would allow a using a more rapid assessment of agonist effects on drug- maintained behavior, if limited data sets can adequately describe this function. The initial studies of the proposal seek to address this issue by comparing these measures of reinforcing efficacy of drugs, using cocaine and fentanyl. Subsequent studies will use these measures to address: l) the nature of the ability of agonists to decrease drug- maintained responding, 2) the relationship between reinforcing efficacy of the treatment drug and the drug for which treatment is sought, 3) the relative abilities of treatment drugs to decrease food- and drug- maintained responding, 4) the ability of agonists from other classes of drug reinforcers as well as receptor-specific agonists and antagonists, to affect drug-maintained responding, 5) how these measures compare with other measures of relative reinforcing efficacy of drugs, and 6) ways in which agonist treatment can be used to permanently decrease drug- maintained behavior.
