The broad objectives of this application are to evaluate oral opioids as reinforcers in rhesus monkeys so that this method of studying drug abuse might eventually be utilized in research in which drug use our the life- course of individual monkeys, in social setting, might be studied. Although there is an abundance of research on the reinforcing effects of orally delivered drugs from a number of drug classes, there has been very little published research on oral opioids as reinforcing stimuli. This is unfortunate because opioid abuse in humans is a problem of long standing, and because the opioid drug class includes such a wide variety of pharmacological tools for further understanding the nature of these drugs as reinforcers. For example, a large number of opioids with similar mechanisms but differing potencies are available for evaluation as oral reinforcers. From these it can be determined whether the rank order potency relationship that has been observed in a number of other preparations will be maintained under conditions in which the drugs are evaluated for the oral reinforcing effects. The effects of weekly administration of an irreversible opioid antagonist on drinking of a selected opioid drug will be observed to assure that the opioid effects are responsible for the consumption of the drug solutions. In an additional group of monkeys, the effects of food-deprivation on establishment and maintenance of opioids as reinforcers will be studied. The role of drug taste in the establishment, maintenance, and extinction of opioid drinking will be studied extensively in the proposed research. A preparation in which taste thresholds can be established is described. Data from studies of taste thresholds with different drugs will provide assistance in interpretation of information about the reinforcing effects of the opioid drugs with different pharmacological potency, but perhaps similar taste qualities. The use of inactive optical isomers of opioids, which should also have taste properties in common with the active isomers, will also help in identifying the role of taste in oral consumption of drugs. Another set of experiments, designed to aid in the interpretation of results of studies on opioids as reinforcing stimuli, involve drug discrimination studies. These will be used to determine the onset and duration of action of orally administered drugs, since onset of drug action may play an important role in determining whether all opioids come to serve as reinforcing stimuli when they are delivered orally.
| Pakarinen, E D; Williams, K L; Woods, J H (1999) Food restriction and sex differences on concurrent, oral ethanol and water reinforcers in juvenile rhesus monkeys. Alcohol 17:35-40 |
| Aspen, J; Gatch, M B; Woods, J H (1999) Training and characterization of a quinine taste discrimination in rhesus monkeys. Psychopharmacology (Berl) 141:251-7 |
| Williams, K L; Pakarinen, E D; Woods, J H (1999) Quadazocine decreases responding reinforced by ethanol, sucrose, and phencyclidine fluid deliveries in rhesus monkeys: comparison to naltrexone's effects. Psychopharmacology (Berl) 144:316-22 |
| Williams, K L; Woods, J H (1998) Oral ethanol-reinforced responding in rhesus monkeys: effects of opioid antagonists selective for the mu-, kappa-, or delta-receptor. Alcohol Clin Exp Res 22:1634-9 |
