The overall goals of this application are: 1) to develop methods for evaluating behavioral and pharmacological treatments for drug abuse and 2) to expand the oral drug self-administration procedures to other phases of the addiction process (e.g., acquisition, relapse) and routes of administration (e.g., smoking). Rhesus monkeys will be trained to consume drugs orally and by inhalation during 3-hr daily sessions. Drug deliveries will be contingent upon responses on lip-operated drinking and smoking spouts.
The specific aims are as follows: 1) To examine factors affecting acquisition of oral drug self-administration. This will serve as an animal model of prevention by testing factors that either slow (e.g., access to nondrug alternative reinforcers) or accelerate (e.g., higher dose, drug history) acquisition; 2) To establish measures of reinforcing efficacy that can be used to evaluate behavioral and pharmacological interventions. Concurrent progressive-ratio (PR) schedules and the behavioral economic analysis of demand (consumption plotted as a function of unit price or responses/mg) will be compared. Both methods provide estimates of maximum response output. The effects of behavioral (alternative reinforcers) and pharmacological treatments on these measures of reinforcing efficacy will be tested. Drug dose/delivery will be varied by changing both concentration and volume to examine the contribution of taste factors. 3) to further examine interactions between feeding conditions and drug self- administration. Food deprivation produces substantial increases in drug intake; however, mechanisms responsible for this relationship are not clear. The hypothesis that acute and/or chronic food deprivation is a form of stress will be examined by blocking the physiological response to stress (corticosterone synthesis). The effects of food deprivation and deprivation of a non-caloric alternative reinforcer will be studied; 4) to continue to investigate self-administration of smoked drugs such as heroin, PCP, THC and nicotine, and combinations of drugs (e.g., cocaine and heroin). Dose response and demand functions will be obtained. Effects of behavioral and pharmacological treatments delivered separately and in combination will be studied as well as the effects of opioid and dopamine agonists and selective antagonists on the demand for heroin, cocaine, and their combination; 5) to investigate reinstatement of extinguished responding (a model of relapse) in monkeys trained to consume oral and smoked heroin. Temporal parameters, feeding conditions, cost of drug and taste vs. postingestional cues will be explored. The health related significance of these studies is that animal models will be refined to test behavioral and pharmacological treatment of behaviors (e.g., acquisition, relapse) that are difficult to study in humans. The results will yield guidelines for evaluating reinforcing effects of drugs and provide information about factors that contribute to prevention and optimal treatment of drug abuse.
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