Unit-price analysis of opioid consumption by monkeys responding under a progressive-ratio schedule of drug injection.

Several reports have indicated that drug consumption in self-administration procedures is a function of the ratio of the instrumental requirement to the dose of drug, a quantity termed unit price. We evaluated three predictions from this unit-price model in a reanalysis of data on opioid self-administration in rhesus monkeys responding under a progressive-ratio schedule (Hoffmeister, 1979). We evaluated whether consumption was inversely related to unit price, and compared the goodness of fit of an equation devised by Hursh, Raslear, Shurtleff, Bauman, and Simmons (1988) to that of a linear model predicting consumption as a function of dose. We also tested whether consumption was constant when the same unit price was comprised of different combinations of dose and instrumental requirement. Consumption declined overall as unit price increased. The equation devised by Hursh et al. and the linear model based on dose fit the data equally well. Drug consumption was not uniform at a given unit price. The analyses suggest limits on the unit-price model as a characterization of drug consumption.     

Normalized demand for drugs and other reinforcers.

The concepts of behavioral economics have proven to be useful for understanding the environmental control of overall levels of responding for a variety of commodities, including reinforcement by drug self-administration. These general concepts have implications for the assessment of abuse liability and drug abuse intervention and the formulation of public policy on drug abuse. An essential requirement is the ability to compare the demand for different drugs directly in order to assess relative abuse liability, and to compare demand for the same drug under different environmental and biological interventions to assess their ability to reduce demand. Until now, such comparisons were hampered by the confounding effect of varying drug doses and potencies that prevent quantitative comparisons of demand elasticity--sensitivity of consumption and responding to the constraint of price (effort). In this paper we describe a procedure to normalize demand-curve analysis that permits dose- and potency-independent comparisons of demand across drugs. The procedure is shown to be effective for comparing drug demand within and across the drug classes. The technique permits a quantitative ordering of demand that is consistent with the peak levels of responding maintained by the drugs. The same technique is generalized for the comparison of other types of reinforcers under different biological conditions.     

Ratio size and cocaine concentration effects on oral cocaine-reinforced behavior.

Monkeys were given a choice between cocaine solutions and water under concurrent fixed-ratio reinforcement schedules. The operant response was spout contact. Six rhesus monkeys served as subjects. The cocaine concentration was varied from 0.0125 to 0.8 mg/ml, and the fixed-ratio value was varied from 8 to 128. Cocaine maintained higher response rates than did water over a wide range of conditions. Response rate and number of cocaine deliveries per session were inverted U-shaped functions of concentration. These functions were shifted to the right as the fixed ratio was increased. The number of cocaine deliveries was more persistent as fixed-ratio value was increased when the unit dose was larger rather than smaller. Cocaine consumption was analyzed as a function of unit price (fixed-ratio value divided by cocaine concentration), and unit price accounted for between 77% and 92% of the variance in cocaine consumption for individual monkeys. The current data support the claim that a drug's reinforcing effects increase directly with dose and underscore the need to gather parametric data when examining the effects of experimental manipulations on a drug-reinforced baseline.     

Oral drug self-administration in rhesus monkeys: interactions between drug amount and fixed-ratio size.

During daily 3-hr sessions, 5 rhesus monkeys drank drug solutions and water that were concurrently available. The drug solutions were: 1 milligram per milliliter (mg/mL) pentobarbital (2 monkeys), 1 mg/mL pentobarbital plus 0.5% ethanol (1 monkey), 1 mg/mL pentobarbital plus 1% ethanol (1 monkey), and 8% ethanol (1 monkey). The drug solution and water were available under identical two-component tandem fixed-ratio continuous-reinforcement N schedules. Two variables were manipulated: the size of the fixed-ratio component and the number of liquid deliveries (N) in the second component. Deliveries of the drug solution maintained higher rates of responding than did deliveries of the drug vehicle, water. The number of drug deliveries per session increased with increases in the number of deliveries per fixed ratio and decreased with increases in fixed-ratio size. Analysis of the results in terms of the proportion of deliveries to responses showed that the number of drug deliveries per session was directly related to the size of this quotient. Finally, when fixed-ratio size was repeatedly doubled, the following orderly relationship emerged: The greater the number of available drug deliveries per fixed ratio, the less was the percent decrease in the number of fixed ratios completed per session. It was concluded that increases in the number of liquid deliveries per fixed ratio resulted in increases in reinforcing efficacy.     

Similar consumption and responding across single and multiple sources of drug

Two experiments were conducted to assess whether total response output and total consumption would be similar when drugs are available from single and multiple sources of reinforcement, as predicted by behavioral economics. In Experiment 1, cigarette-deprived smokers were exposed to a concurrent-chains schedule in which equal fixed-ratio schedules served as the initial links, and different reinforcer magnitudes (i.e., number of cigarette puffs) were arranged across alternatives. After the session, obtained unit price was calculated and imposed in the next session when a different number of puffs was available according to a single fixed-ratio schedule. Thus, the unit price at which cigarette puffs could be earned was yoked within subjects across the single and concurrent-chains schedules. When plotted as a function of unit price, similar consumption and response rates were usually obtained across these schedules. Experiment 2 addressed a weakness of Experiment 1, namely, that responding was allocated exclusively to the larger reinforcer magnitude in concurrent-chains conditions, and therefore this schedule may have functioned as a single schedule. In Experiment 2, subjects were instructed to alternate responding between the two alternative schedules. Instructions produced approximately equal response allocation between the two alternatives. Again, similar consumption and response rates were observed across the single and instructed concurrent-chains schedules. These findings are discussed in the context of direct effects and behavioral economics perspectives of drug self-administration.     

Cocaine and food as reinforcers: effects of reinforcer magnitude and response requirement under second-order fixed-ratio and progressive-ratio schedules.

Reinforcer magnitude and fixed-ratio requirement were varied under two second-order schedules. Under one, the first sequence of a fixed number of responses completed after the lapse of a 10-min fixed interval produced reinforcement. Under the second, a second-order progressive-ratio schedule, the fixed number of responses increased after each reinforcement. Either cocaine (0 to 300 micrograms/kg/inj) or food (0 to 5,700 mg/delivery) reinforcers were delivered. Under some conditions, a 2-s illumination of stimulus lights occurred on completion of each ratio sequence. Under the second-order schedule, as cocaine dose or amount of food increased, rates of responding increased; at the highest values, rates of responding decreased. Increases in the ratio requirement from 10 to 170 responses minimally decreased overall response rates. Under the second-order progressive-ratio schedule, increases in dose of cocaine or amount of food increased rates of responding; at the highest amounts of food, rates of responding decreased but response rates at the highest dose of cocaine remained relatively high. The highest ratio requirement that was completed (breaking point) depended on the dose of cocaine but was less dependent on the amount of food. Removing brief-stimulus presentations had a greater effect on completion of ratio requirements with cocaine compared to food.