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.     

Concurrent phencyclidine and saccharin access: presentation of an alternative reinforcer reduces drug intake.

Six monkeys self-administered orally delivered phencyclidine ("angel dust") and saccharin under concurrent fixed-ratio 16 schedules during daily three-hour sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. Three saccharin concentrations (0.003%, 0.03% and 0.3%, wt/vol) were tested in a nonsystematic order. For each saccharin concentration, the following series of phencyclidine concentrations (mg/ml) was presented: 0.25, 0.5, 1, 0.25 (retest), 0.125, 0.0625, 0.0312, 0.25 (retest) and 0 (water with stimuli signaling phencyclidine). As the saccharin concentration increased, the number of drug deliveries decreased, and the peaks of the concentration-response functions were shifted to the right. The lowest saccharin concentration (0.003%, wt/vol) maintained responding in excess of phencyclidine levels in only one monkey. The two higher saccharin concentrations maintained behavior far in excess of phencyclidine, but saccharin deliveries decreased in some monkeys as phencyclidine concentration and intake (mg/kg) increased. The time course and patterns of phencyclidine-reinforced responding were also altered when saccharin was concurrently available. The results are discussed in terms of strategies to reduce drug-reinforced behavior, preference between different reinforcers, and measures of reinforcing efficacy.     

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.     

Food and amphetamine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or fluid solutions were examined in 6 adult male baboons (Papio cynocephalus anubis). During daily 23-hr experimental sessions, baboons had concurrent access to both food pellets and fluid, with responding maintained under fixed-ratio schedules of reinforcement that varied between the two commodities. The fixed-ratio requirement, or cost, for pellets was increased when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.002 mg/kg d-amphetamine, or (d) 0.004 mg/kg d-amphetamine was available. When given nonrestricted concurrent access to food pellets and amphetamine at minimal cost (FR 2), baboons self-administered sufficient amphetamine to decrease pellet intake. Increasing the response requirement for pellets decreased pellet intake at a similar rate regardless of the available fluid and increased fluid intake in a variable manner among baboons such that there were no statistically significant increases in fluid intake. In contrast, when access to pellets was restricted to 70% of maximal intake under nonrestricted conditions, increasing pellet cost decreased pellet intake and increased fluid intake more rapidly when the high amphetamine dose was available. Thus, amphetamine was more effective as an economic substitute for pellets when access to pellets was restricted. The response cost for vehicle and both amphetamine concentrations was increased when baboons had nonrestricted and restricted access to pellets. Increasing the response requirement for fluid delivery decreased intake of all three fluids similarly under both pellet-access conditions. The results indicate that substitution between commodities with minimal commonalities can be studied under controlled laboratory conditions and is dependent upon reinforcement schedule and commodity restrictions.     

Effects of body weight on discriminative-stimulus control by phencyclidine in the pigeon.

Using a color-tracking procedure with responses reinforced under a second-order schedule, the discriminative-stimulus properties of phencyclidine were studied in pigeons maintained at 70%, 80%, or 90% of their free-feeding weights. The generalization curves for phencyclidine were similar at all three body weights. Generalization curves for pentobarbital, d-amphetamine, and saline were also unrelated to body weight. These data suggest that food deprivation may not influence the discriminative-stimulus properties of drugs in the way that it influences the reinforcing-stimulus properties of drugs. The reason may be that during discrimination training interoceptive stimuli resulting from food deprivation do not become conditioned to the stimulus properties of the drug, because the food-deprivation stimuli are paired equally often with the presence and absence of drug stimuli.     

Chlordiazepoxide effects on ethanol self-administration: dependence on concurrent conditions.

Experiments examined the effects of acute doses of chlordiazepoxide upon ethanol self-administration in the rat. A concurrent-schedule procedure was used that employed choice between ethanol (5%) and a second fluid (either water or a 1% sucrose solution). When ethanol and water were the available fluids, chlordiazepoxide at doses of 15 and 20 mg/kg reduced ethanol-reinforced responding and intake, with a greater reduction occurring at the 20 mg/kg dose. However, when ethanol and sucrose were concurrently available, in many rats only the 20 mg/kg dose of chlordiazepoxide reduced ethanol-reinforced responding. The differences in dose response function occurred in most animals without large changes in the baseline ethanol-reinforced responding across the two concurrent conditions. Thus the dose-effect curve relating chlordiazepoxide and ethanol self-administration can be altered, dependent upon the nature of the concurrently available reinforcers.     

Priming effects with food and water reinforcers in hamsters

Hamsters were tested in a square maze with either food or water in each corner compartment. A substantial priming effect (runway times increase as intertrial interval increases) was demonstrated using both food and water reinforcers. A lengthy period of free access to food and water (satiation) immediately abolished the priming effect, although runway times in general remained relatively rapid for some time. Extinction of rapid runway times proceeded more slowly under food than under water deprivation. It is concluded that priming is a widespread phenomenon associated with the presentation of a reinforcing stimulus to an appropriately deprived animal.     

ESTABLISHING OPERATIONS AND REINFORCEMENT EFFECTS

Positive reinforcement procedures have had a major impact on educational programs for the developmentally disabled; nevertheless, variation in reinforcer effectiveness both within and across individuals is a common phenomenon. This study examined one class of variables—establishing operations—that might influence the effectiveness of reinforcers. Five developmentally disabled adult males participated. Responding on one of two motor tasks—switch closure or block placement—was assessed during baseline, satiation, and deprivation conditions with respect to three classes of consequences: small food items, music, and social praise. Deprivation and satiation conditions were constructed so as not to alter significantly the normal course of events in a subject's day. For example, food deprivation entailed scheduling sessions just prior to a subject's regular lunch, and social deprivation involved limiting a subject's access to social interaction for 15 minutes, during which time the subject had access to an assortment of other activities. Results showed that each stimulus class functioned as reinforcement with different degrees of effectiveness during satiation versus deprivation conditions. These results are discussed in light of previous research on enhancement of reinforcer efficacy as well as the assessment and identification of functional reinforcers, and implications are presented for future research and client habilitation.     

Interactions between the effects of food and water motivating operations on food‐ and water‐reinforced responding in mice

Two experiments examined interactions between the effects of food and water motivating operations (MOs) on the food‐ and water‐reinforced operant behavior of mice. In Experiment 1, mice responded for sucrose pellets and then water reinforcement under four different MOs: food deprivation, water deprivation, concurrent food and water deprivation, and no deprivation. The most responding for pellets occurred under food deprivation and the most responding for water occurred under water deprivation. Concurrent food and water deprivation decreased responding for both reinforcers. Nevertheless, water deprivation alone increased pellet‐reinforced responding and food deprivation alone likewise increased water‐reinforced responding relative to no deprivation. Experiment 2 demonstrated that presession food during concurrent food and water deprivation increased in‐session responding for water relative to sessions where no presession food was provided. Conversely, presession water during concurrent food and water deprivation did not increase in‐session responding for pellets. These results suggest that a) the reinforcing value of a single stimulus can be affected by multiple MOs, b) a single MO can affect the reinforcing value of multiple stimuli, and c) reinforcing events can also function as MOs. We consider implications for theory and practice and suggest strategies for further basic research on MOs.     

Substitution and caloric regulation in a closed economy.

Three experiments were conducted to study the effect of an imperfect substitute for food on demand for food in a closed economy. In Experiments 1 and 2, rats pressed a lever for their entire daily food ration, and a fixed ratio of presses was required for each food pellet. In both experiments, the fixed ratio was held constant during a daily session but was increased between sessions. The fixed ratio was increased over a series of daily sessions once in the absence of concurrently available sucrose and again when sucrose pellets were freely available. For both series, increases in the fixed ratio reduced food intake, but body weight was reduced only in the no-sucrose condition. In the sucrose condition, body weight and total caloric intake (sucrose plus food) were relatively unaffected by increases in the fixed ratio. At all fixed ratios, food intake was proportionally reduced by the intake of sucrose. In Experiment 3, monkeys obtained food or saccharin by pressing keys; the fixed ratio of presses per food pellet was increased once when tap water was each monkey's only source of fluid, again when each monkey's water was sweetened with saccharin, and a third time when each monkey had concurrent access to the saccharin solution and plain water. Increases in the fixed ratio, but not the intake of the saccharin solution, reduced each monkey's food intake. Because neither rats' sucrose nor monkeys' saccharin intakes affected the slope of the respective demand curves for food, monkeys and rats increased their daily output of presses and thereby defended their daily intake of those complementary elements of food. However, sucrose reduced rats' food intake. The relative constancy of body weight and total caloric intake in the sucrose condition is consistent with the possibility that rats tended to regulate caloric intake.     

Food and cocaine self-administration by baboons: effects of alternatives.

The effects of the availability of an alternative reinforcer on responding maintained by food pellets or drug solutions were examined in 8 adult male baboons (Papio hamadrayas anubis). During daily 23-hr experimental sessions, baboons had access to both food pellets and fluid under a two-choice procedure, in which the response requirement, under a fixed-ratio schedule, differed for the two commodities. There were no restrictions on access to water, which was continuously available from a spout at the rear of each cage. In Experiment 1, the fixed-ratio requirement, or cost, for fluid delivery remained constant while the fixed-ratio requirement for pellets was changed every 2 or 3 days when (a) no fluid, (b) a dilute dextrose vehicle, (c) 0.008 mg/kg per delivery cocaine, (d) 0.016 mg/kg per delivery cocaine, or (e) 0.032 mg/kg per delivery cocaine was available concurrently. In Experiment 1, progressively increasing the response requirement for pellets decreased pellet intake, but for 4 baboons pellet intake at maximum pellet cost was lower when cocaine, compared to the vehicle, was available. Increasing the response requirement for pellets had variable effects on vehicle intake. However, increasing the response requirement for pellets increased intake of at least one dose of cocaine to a greater extent than vehicle in all 8 baboons. Thus, cocaine could be considered a more effective economic substitute than vehicle for pellets. Experiment 2 systematically varied the order in which the response requirements for a pellet delivery were presented and added a control condition in which cocaine doses, yoked to the amount self-administered, were given three times during the session by the experimenter. Again, pellet intake at maximal pellet cost was lower when cocaine, compared to the vehicle, was available. In contrast, experimenter-given cocaine doses did not alter responding maintained by pellets. Thus, the effects of self-administered cocaine on responding maintained by food pellets differed from the effects of experimenter-given cocaine on responding maintained by food pellets.     

Food and water intake as functions of resource consumption costs in a closed economy.

In two experiments, rats living in a closed economy were offered continuous, concurrent access to four resources: food, water, a nest, and a running wheel. Costs of consuming food and water were imposed with bar-press requirements, and the price of either one or both resources was raised. As the consumption cost increased, less was consumed in each bout of resource use. Bout frequency increased, but not sufficiently to compensate for the fall in bout size, and total intake fell. Food and water tended to be complementary resources, in that as intake of one fell with its price, intake of the other also decreased. This interaction was accounted for by the defense of the ratio of body water to lean body mass. As amount consumed decreased, increases in feed efficiency (weight gain per unit of food ingested) and the use of stored calories compensated for the reduced energy intake. There was evidence of competition between feeding and drinking at the higher costs: When both commodities were expensive, the decline in the intake of each one was greater than when only one commodity was expensive. Although the time spent nesting, running, and in unmonitored activity was adjusted when feeding or drinking took more of the rat's day, there was no particular activity that was sacrificed.     

The effect of hunger on water intake in rats

Although reciprocal inhibition between eating and drinking has been postulated, the commonly observed reduction of water intake by hungry rats may not be due to any direct inhibitory mechanism. In one experiment rats deprived of food for 24 hr. and then injected with 2 ml. of NaCl drank the same as rats that had received food ad lib. In the second experiment a stomach load of 10 ml. of water 3 hr. before the salt injection was designed to abolish any water deficit that might have occurred during food deprivation had there been inhibition of drinking by hunger. Here again rats deprived of food did not drink less than undeprived animals. In fact the hungry rats drank slightly but significantly more. This phenomenon may be related to the observation confirmed here that during food deprivation rats excrete about twice as much rather dilute urine as during ad lib food intake. This seems to indicate that though in general food deprived rats drink less than normal they actually drink more than they need. Schedule induced polydipsia also occurs during food deprivation and this too makes it unlikely that water-intake is actually inhibited during hunger.     

Inhibition of ad Libitum Feeding in Rats by Salt Injections and Water Deprivation

Inhibition of ad libitum feeding in rats was induced by hypertonic NaCl injections. Though osmotic loads of sufficient size were capable of abolishing feeding completely for a time, the effect was not as large as had been predicted from a hypothesis of strictly linear subtractive inhibition. Feeding at a low level of hunger seems to be somewhat less affected by osmotic inhibition than feeding on a deprivation schedule. Inhibition of feeding was also produced by deprivation of water, and both the inhibition of food intake during deprivation, and the disinhibition by subsequent drinking indicated that the amount of inhibition of food intake is a non-linear (accelerating) function of water deficit. A model of the process indicating that the thirst signal undergoes a non-linear transformation before being subtracted from the signal corresponding to food demand is proposed.     

Bouts of responding on variable-interval schedules: effects of deprivation level

Rats obtained food pellets on a variable-interval schedule of reinforcement by nose poking a lighted key. After training to establish baseline performance (with the mean variable interval set at either 60, 120, or 240 s), the rats were given free access to food during the hour just before their daily session. This satiation operation reduced the rate of key poking. Analysis of the interresponse time distributions (log survivor plots) indicated that key poking occurred in bouts. Prefeeding lengthened the pauses between bouts, shortened the length of bouts (less reliably), and had a relatively small decremental effect on the response rate within bouts. That deprivation level affects mainly between-bout pauses has been reported previously with fixed-ratio schedules. Thus, when the focus is on bouts, the performances maintained by variable-interval schedules and fixed-ratio schedules are similarly affected by deprivation.     

Deprivation and satiation: The interrelations between food and wheel running

Two experiments were designed to assess whether depriving rats of food would increase the reinforcement effectiveness of wheel running (Experiment 1) and whether satiation for wheel running would decrease the reinforcement effectiveness of food (Experiment 2). In Experiment 1, a progressive-ratio schedule was used to measure the reinforcement effectiveness of wheel running when rats were deprived or not deprived of food. Completion of a fixed number of lever presses released a brake on a running wheel for 60 s, and the response requirement was systematically increased until the rat stopped pressing or until 8 hr had elapsed. The ratio value reached (and the total number of lever presses) was an inverted-U function of food deprivation (percentage body weight). In Experiment 2, when wheel running preceded test sessions, fewer food-reinforced lever presses were maintained by the progressive-ratio schedule, and responding occurred at a lower rate on a variable-interval schedule. An interpretation of these results is that deprivation or satiation with respect to one event (such as food) alters the reinforcement effectiveness of a different event (such as access to wheel running).     

Food-deprivation level alters the effects of morphine on pigeons'' key pecking.

Four pigeons pecked response keys under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. Components alternated separated by 15-s timeouts; each was presented six times. Pigeons were maintained at 70%, 85%, and greater than 90% of their free-feeding weights across experimental conditions. When response rates were stable, the effects of morphine (0.56 to 10.0 mg/kg) and saline were investigated. Morphine reduced response rates in a dose-dependent manner under the fixed-ratio schedule and at high doses under the fixed-interval schedule. In some cases, low doses of morphine increased rates under the fixed-interval schedule. When pigeons were less food deprived, reductions in pecking rates occurred at lower doses under both schedules for 3 of 4 birds compared to when they were more food deprived. When pigeons were more food deprived, low doses of morphine increased rates of pecking in the initial portions of fixed intervals by a greater magnitude. Thus, food-deprivation levels altered both the rate-decreasing and rate-increasing effects of morphine. These effects may share a common mechanism with increased locomotor activity produced by drugs and with increased drug self-administration under conditions of more severe food deprivation.     

Drug discrimination under a concurrent fixed-ratio fixed-ratio schedule.

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-ratio 10 fixed-ratio 40 schedule of food presentation, in which the fixed-ratio component with the lower response requirement was programmed to reinforce responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized, pigeons averaged 98% of their responses on the pentobarbital-biased key during training sessions preceded by pentobarbital, and they averaged 90% of their responses on the saline-biased key during training sessions preceded by saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, or ethanol, pigeons switched from responding on the saline-biased key at low doses to responding on the pentobarbital-biased key at higher doses (the dose-response curve was quantal). High doses of phencyclidine produced responding on both keys, whereas pigeons responded almost exclusively on the saline-biased key after all doses of methamphetamine. These and previous experiments using concurrent reinforcement schedules to study drug discrimination illustrate that the schedule of reinforcement is an important determinant of the shape of dose-effect curves in drug-discrimination experiments.     

The effects of chronic water deprivation on metabolic rate and long-trace taste-aversion conditioning in rats

The effect of chronic water deprivation on metabolic rate and long-trace taste-aversion conditioning was examined in Wistar-derived rats. Subjects were either maintained on a water deprivation regimen or allowed free access to water for a seven-week period prior to conditioning. At conditioning, rats were presented a saccharin CS followed 0-, 45-, 90-, or 180-min later by an i.p. injection of LiCl. Additionally, pseudo-conditioned groups were presented the CS followed immediately by an injection of physiological saline. Heightened oxygen consumption in deprived subjects suggested that chronic water deprivation increased metabolic rate. While no differences in the amount of saccharin intake were observed at conditioning, percent preference for saccharin scores during a 24-h two-bottle water/saccharin test revealed that non-chronically deprived rats supported conditioning at longer CS-US intervals than did chronically water-deprived rats. Results are interpreted in terms of a time-contraction effect stemming from an alteration of an internal metabolic count-down timer.     

Stimulus control of cocaine self-administration

Environmental stimuli that set the occasion wherein drugs are acquired can "trigger" drug-related behavior. Investigating the stimulus control of drug self-administration in laboratory animals should help us better understand this aspect of human drug abuse. Stimulus control of cocaine self-administration was generated here for the first time using multiple and chained schedules with short, frequently-alternating components--like those typically used to study food-maintained responding. The procedures and results are presented along with case histories to illustrate the strategies used to produce this stimulus control. All these multicomponent schedules contained variable-interval (VI) components as well as differential-reinforcement-of-other-behavior (DRO) or extinction components. Schedule parameters and unit dose were adjusted for each rat to produce stable, moderate rates in VI components, with minimal postreinforcement (infusion) pausing, and response cessation in extinction and DRO components. Whole-body drug levels on terminal baselines calculated retrospectively revealed that all rats maintained fairly stable drug levels (mean, 2.3 to 3.4 mg/kg) and molar rates of intake (approximately 6.0 mg/kg/hr). Within this range, no relation between local VI response rates and drug level was found. The stimulus control revealed in cumulative records was indistinguishable from that achieved with food under these schedules, suggesting that common mechanisms may underlie the control of cocaine- and food-maintained behavior.