Concurrent access to two concentrations of orally delivered phencyclidine: effects of feeding conditions.

Two experiments addressed the effects of food satiation and deprivation on oral self-administration of two concurrently available phencyclidine concentrations. In the first experiment, 8 rhesus monkeys self-administered either of two concentrations of phencyclidine ("PCP, angel dust") and water under concurrent fixed-ratio 16 schedules. One concentration was always held constant (0.25 mg/mL) while a series of other phencyclidine concentrations, ranging from 0 (water) to 1.0 mg/mL, was presented in a nonsystematic order. Initially the monkeys were tested while food satiated, and the procedure was then repeated during food deprivation. The monkeys usually selected the higher concentration within the first few minutes of the session, indicating that taste and/or other immediate postingestional effects were important factors. Contrary to a number of previous reports, there were no consistent differences across subjects in the mean number of liquid deliveries or mean drug intake (mg/kg) during food satiation and deprivation. However, for all monkeys the within-session time course of responding during food satiation consistently differed from that during deprivation. A second experiment assessed whether the failure to find consistent differences in drug intake during food satiation and deprivation had been due to the history of concurrent access to different phencyclidine concentrations or to the extended experience with phencyclidine under food-satiation conditions. Six additional monkeys (Group 2) were exposed to the phencyclidine self-administration procedure (during food satiation and deprivation) for the same length of time as the monkeys in Experiment 1 (Group 1), except they received only concurrent access to phencyclidine (0.25 mg/mL) and water. Both groups then received concurrent access to phencyclidine and water during five repeated cycles of food deprivation and satiation. There were also marked individual differences in Group 2: During food satiation, 2 of the monkeys' responding increased, 1 showed no change, and 3 decreased. Examination of a number of historical variables indicated that the greater the percentage of total sessions spent during food satiation with phencyclidine available (before these experiments began), the greater the amounts of phencyclidine consumed during food satiation and the smaller the differences in phencyclidine intake when the two feeding conditions were compared.     

Modifying drug-reinforced behavior by altering the economic conditions of the drug and a nondrug reinforcer.

Six rhesus monkeys were trained to self-administer orally delivered phencyclidine (0.25 mg/mL) and saccharin (0.03% wt/vol) under concurrent fixed-ratio 16 schedules. In Condition 1 the fixed-ratio requirement for phencyclidine was changed from 16 to 4, 8, 16, 32, 64, 128 and 16 while the fixed-ratio requirement for saccharin deliveries remained constant at 16. In Condition 2 the fixed-ratio value for saccharin was systematically altered while the fixed-ratio requirement for phencyclidine remained at 16, and in Condition 3 the fixed-ratio requirements for both phencyclidine and saccharin were altered simultaneously. Water was then substituted for saccharin, and the series of fixed-ratio manipulations was replicated. The phencyclidine concentration was reduced to 0.125 mg/mL and Conditions 1 and 3 were repeated. When the fixed-ratio requirement for phencyclidine was increased and the fixed-ratio requirement for saccharin or water remained fixed at 16, phencyclidine deliveries decreased when saccharin (vs. water) was concurrently available. The magnitude of the decrease ranged from 20% to 90% (of the concurrent water condition) as the fixed-ratio requirement for phencyclidine increased from 4 to 128. When the fixed-ratio requirement for phencyclidine remained at 16 and the fixed-ratio requirements for concurrent saccharin or water varied between 4 and 128, phencyclidine deliveries decreased by 30% to 40% due to the concurrent availability of saccharin (vs. water). This decrease occurred only at the three lowest fixed-ratio values when saccharin intake was relatively high. When the fixed-ratio requirements for both phencyclidine and concurrent saccharin or water were varied simultaneously, phencyclidine deliveries were reduced from 20% to 45% when saccharin (vs. water) was concurrently present. There was little effect of reducing the phencyclidine concentration when the data were analyzed in terms of unit price (responses per milligram). Thus, changes in the fixed-ratio requirement or drug concentration were functionally similar, and unit price of phencyclidine was the variable that was influenced by the presence of concurrent saccharin. These data indicate that drug-reinforced behavior is substantially reduced when the environment is enriched with an alternative nondrug reinforcer. The economic context in which these substances are presented is an important determinant of drug-reinforced behavior.     

Pentobarbital self-administration in rhesus monkeys: drug concentration and fixed-ratio size interactions.

Performances of three rhesus monkeys were reinforced by the oral delivery of pentobarbital and studied as functions of fixed-ratio size and drug concentration. Pentobarbital solutions and water were concurrently available on identical reinforcement schedules from separate liquid-delivery systems during 3-hour sessions. Under a fixed-ratio 16 schedule of drug availability, a descending series of drug concentrations was tested (4, 2, 1, 0.5, 0.25, 0.125, and 0.0625 mg/ml, followed by a retest at 4 mg/ml). Partial concentration series beginning with the highest concentration were repeated with fixed-ratios of 32 and 64, with a fixed-ratio 128 for two monkeys, and with fixed-ratio 256 for one. At each fixed-ratio value, response rate and number of drug deliveries were inverted U-shaped functions of pentobarbital concentration. Drug intake (mg/kg/session) increased directly with drug concentration. As the fixed-ratio size was increased, the number of liquid deliveries decreased. For each drug concentration, when the numbers of drug deliveries at fixed-ratios of 32, 64, and 128 responses were plotted as percentages of those obtained at fixed-ratio 16, the following orderly relationship emerged: the higher the drug concentration, the less that drug deliveries were decreased by increases in fixed-ratio size. This relationship indicates an increase in reinforcing efficacy with increases in pentobarbital concentration.     

Oral self-administration of pentobarbital by rhesus monkeys: relative reinforcing effects under concurrent fixed-ratio schedules.

During daily 3-hr sessions, orally delivered pentobarbital solutions and water, or two separate pentobarbital solutions, were concurrently available to rhesus monkeys according to fixed-ratio schedules of mouth contacts with a spout. First water, and then each of four "comparison-concentration" pentobarbital solutions (0.0625, 0.25, 1, and 4 mg/mL), was successively available from one spout for a block of sessions under a fixed-ratio-64 (three monkeys) or fixed-ratio-16 (one monkey) schedule. Under an identically sized fixed-ratio schedule, deliveries of a "standard-concentration" pentobarbital solution were concurrently available from a second spout. The concentration of the standard solution remained unchanged throughout testing of the series of comparison solutions. Each of three pentobarbital concentrations (4, 1, and 0.25 mg/mL) in turn served as the standard concentration. Within each pair of concurrently available solutions, the higher drug concentration maintained more behavior than the lower concentration. Thus when monkeys were provided with concurrent access to different pentobarbital concentrations, relative reinforcing effects were directly related to drug concentration. Further, the amount of behavior maintained by a particular drug concentration was dependent on the concentration of the concurrently available drug solution. Thus, the relative effectiveness of a reinforcer in maintaining behavior is a function of both the reinforcer's magnitude and the availability of alternative reinforcers in the environment.     

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.     

Oral self-administration of pentobarbital by rhesus monkeys: maintenance of behavior by different concurrently available volumes of drug solution.

For 4 rhesus monkeys, mouth-contact responses with either of two brass spouts were reinforced according to fixed-ratio schedules by 0.65-mL liquid deliveries during daily 3-hr sessions. Three experiments were conducted. In each experiment, independent fixed-ratio schedules were concurrently in effect at the two spouts. Following completion of each fixed ratio on a spout, a specified number of liquid deliveries were available from that spout under a continuous-reinforcement schedule. The number of such deliveries available at each spout was manipulated independently. In Experiment 1, a 1-mg/mL pentobarbital solution was simultaneously available with water (the drug vehicle) under concurrent fixed-ratio schedules of 32 responses for 3 subjects and 64 responses for the remaining subject. The number (N) of liquid deliveries that were available after completion of each fixed ratio was varied in the following order: 8, 4, 2, 1, and 8 (retest). For each subject at each condition, drug maintained more responding than water. The number of drug deliveries obtained per session was directly related to the amount of drug available per fixed ratio (i.e., to N), whereas the number of fixed ratios completed per session generally was inversely related to the value of N. In Experiment 2, fixed-ratio size was the same for each subject as in Experiment 1, but deliveries of a 1-mg/mL pentobarbital solution were available at both spouts. The number of drug deliveries available under one fixed-ratio schedule (Ns, the "standard" reinforcer amount) was held at eight, and the number of drug deliveries available under the second schedule (Nc, the "comparison" reinforcer amount) was changed across blocks of six sessions of stable responding in the following order: 1, 2, 4, 8, 4, 2, and 1. The identical series of comparison reinforcer amounts (Nc) was then tested twice more, but with the standard reinforcer (Ns) held first at four and then at two deliveries. Across the three choice series, reinforcing effects were directly related to reinforcer magnitude. In Experiment 3, deliveries of a 1-mg/mL pentobarbital solution again were available at both spouts. However, the two reinforcer amounts were held constant at N = 8 deliveries under one schedule and N = 4 deliveries under the second schedule, and fixed-ratio size was systematically varied. Across the range of fixed-ratio sizes from low to high, the degree to which behavior was better maintained by the larger of the two drug quantities was an inverted U-shaped function of fixed-ratio size.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.     

Matching under nonindependent variable-ratio schedules of drug reinforcement.

Response-contingent deliveries of oral pentobarbital maintained responding of 3 rhesus monkeys during daily 3-hr sessions. Deliveries of pentobarbital were arranged under nonindependent concurrent variable-ratio variable-ratio schedules. Responses to either schedule counted toward completion of both variable-ratio schedule requirements. This schedule is similar in some respects to conventional concurrent variable-interval variable-interval schedules, in which passage of time counts toward completion of the interval value on both schedules. Restricted nonindependent concurrent variable-ratio variable-ratio schedules were also studied. On that schedule, when a drug delivery was assigned to one spout, it had to be collected before responses on the opposite spout again counted toward completion of the schedule requirements. Relative reinforcer magnitude was varied by changing the drug concentration on one schedule while keeping the drug concentration constant on the other variable-ratio schedule. Under both types of concurrent variable-ratio schedules, the relative rate of responding corresponded to the relative drug intake. Unlike earlier studies of concurrent variable-interval variable-interval intravenous cocaine reinforcement, preference was proportionate to concentration, and exclusive preferences did not develop. The relationship between relative rate of responding and relative drug intake was well described by the generalized matching law.     

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.     

Relative reinforcer magnitude under a nonindependent concurrent schedule of cocaine reinforcement in rhesus monkeys.

Lever pressing by three rhesus monkeys was maintained under a two-lever concurrent schedule of cocaine reinforcement. Responding on one lever (constant-dose lever) produced a constant dose of 0.05 or 0.1 mg/kg/injection arranged according to a variable-interval 1-min schedule. Responding on the other lever (variable-dose lever) produced a comparison dose of cocaine (0.013 to 0.8 mg/kg/injection), also under a variable-interval 1-min schedule. The two variable-interval schedules were made nonindependent by arranging that the assignment of a reinforcer by one schedule inactivated the second schedule until the assigned reinforcer had been obtained. This modification ensured that the two cocaine doses were obtained with approximately equal frequency, regardless of the distribution of the subject's responding. Preference, indicated by relative response frequency on the variable-dose lever, was almost always for the larger of the doses and was a monotonic function of the comparison dose, except at the highest doses. Preferences at the highest comparison doses may have resulted from the low overall response rates exhibited at these doses. Relative response frequencies on the variable-dose lever roughly matched relative reinforcer magnitude (mg/kg/injection available on the variable-dose lever divided by the sum of mg/kg/injections available on each lever).     

Reinforcement magnitude: an evaluation of preference and reinforcer efficacy

Consideration of reinforcer magnitude may be important for maximizing the efficacy of treatment for problem behavior. Nonetheless, relatively little is known about children's preferences for different magnitudes of social reinforcement or the extent to which preference is related to differences in reinforcer efficacy. The purpose of the current study was to evaluate the relations among reinforcer magnitude, preference, and efficacy by drawing on the procedures and results of basic experimentation in this area. Three children who engaged in problem behavior that was maintained by social positive reinforcement (attention, access to tangible items) participated. Results indicated that preference for different magnitudes of social reinforcement may predict reinforcer efficacy and that magnitude effects may be mediated by the schedule requirement.     

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.     

Choice between sequences of fixed-ratio schedules: effects of ratio values and probability of food delivery.

Pigeons were exposed to schedules of food delivery that consisted of two sequential fixed ratios. When alternative sequences provided two food deliveries per 50 responses, the schedule with the shorter initial fixed-ratio value was consistently preferred. Progressively reducing from 1.0 to .25 the probability of food delivery following completion of the second fixed ratio of the sequence with the shorter initial fixed ratio did not reduce preference for this sequence. Moreover, the sequence with the shorter initial fixed ratio also was preferred when the probability of food delivery following completion of the initial ratio in that sequence was progressively reduced from 1.0 to .5, although preference shifted to the alternative when the probability was reduced to 0. These findings suggest that the length of the initial fixed ratio was a primary determinant of choice. Subsequent manipulations demonstrated, however, that when the initial fixed ratios of the two alternatives were equal, changes in the ratio value and probability of food delivery following completion of the second fixed ratio lawfully affected choice.     

Schedules of food postponement: II. Maintenance of behavior by food postponement and effects of the schedule parameter

In Experiment I, food-deprived, feeder-trained squirrel monkeys pressed a lever to postpone brief electric shocks (Response-Shock=Shock-Shock interval=30 seconds). Forty-one three-hour sessions of shock postponement were followed by 120 sessions of concurrent shock and food postponement. The shock schedule was unchanged and the food schedule was Response-food interval–20 seconds, Food-food interval 10 seconds. After concurrent shock and food postponement, the shock schedule was discontinued and 40 sessions of food postponement ensued, followed by 53 sessions of extinction. After extinction, food postponement was resumed for 11 sessions. Stable responding with low food rates was maintained under food-postponement after the concurrent schedule. Responding decreased to low levels under extinction and recovered immediately to previous levels when the food-postponement schedule was re-instated. In Experiment II, a parameter of the food-postponement schedule was studied sequentially. Using the same subjects, the Response-food–Food-food interval was manipulated from four seconds to 80 seconds with several orders of presentation. Relations of response rates and food rates to the parameter were similar to those seen under shock postponement. Exposure to very short postponement times (four seconds), resulting in very high food rates, decreased but did not abolish subsequent responding at longer postponement times. Results are discussed from the point of view that reinforcing functions of stimuli consequent on responding depend on a prior history of scheduled contact with those stimuli.