Behavior controlled by scheduled injections of cocaine in squirrel and rhesus monkeys.

Rates and patterns of key-press responding maintained under schedules in which responding resulted in intravenous injections of cocaine were studied in squirrel monkeys and rhesus monkeys. Each injection was followed by a 60- or 100-sec timeout period. Schedule-controlled behavior was obtained at appropriate cocaine doses in each species. Under FR 10 or FR 30 schedules, performance was characterized by high rates of responding (usually more than one response per second) in each ratio. Under FI 5-min schedules, performance was characterized by an initial pause, followed by acceleration of responding to a final rate that was maintained until the end of the interval. Under multiple fixed-ratio fixed-interval schedules, rates and patterns of responding appropriate to each schedule component were maintained. Responding seldom occurred during timeout periods under any schedule studied. At doses of cocaine above or below those that maintained characteristic schedule-controlled behavior, rates of responding were relatively low and patterns of responding were irregular. Characteristic fixed-interval responding was maintained over a wider range of cocaine doses than characteristic fixed-ratio responding. Complex patterns of responding controlled by discriminative stimuli under fixed-ratio or fixed-interval schedules can be maintained by cocaine injections in squirrel monkeys and rhesus monkeys.     

Effects of cocaine on performance under fixed-interval schedules with a small tandem ratio requirement

Daily administration of cocaine often results in the development of tolerance to its effects on responding maintained by fixed-ratio schedules. Such effects have been observed to be greater when the ratio value is small, whereas less or no tolerance has been observed at large ratio values. Similar schedule-parameter-dependent tolerance, however, has not been observed with fixed-interval schedules arranging comparable interreinforcement intervals. This experiment examined the possibility that differences in rate and temporal patterning between the two types of schedule are responsible for the differences in observed patterns of tolerance. Five pigeons were trained to key peck on a three-component multiple (tandem fixed-interval fixed-ratio) schedule. The interval values were 10, 30, and 120 s; the tandem ratio was held constant at five responses. Performance appeared more like that observed under fixed-ratio schedules than fixed-interval schedules. Effects of various doses of cocaine given weekly were then determined for each pigeon. A dose that reduced responding was administered prior to each session for 50 days. A reassessment of effects of the range of doses revealed tolerance. The degree of tolerance was similar across components of the multiple schedule. Next, the saline vehicle was administered prior to each session for 50 days to assess the persistence of tolerance. Tolerance diminished in all subjects. Overall, the results suggested that schedule-parameter-dependent tolerance does not depend on the temporal pattern of responding engendered by fixed-ratio schedules.     

A comparison of responding maintained under second-order schedules of intramuscular cocaine injection or food presentation in squirrel monkeys.

Key pressing by squirrel monkeys was maintained under second-order schedules of either intramuscular cocaine injection or food presentation. Under one schedule, each completion of a 10-response fixed-ratio unit produced a brief visual stimulus; the first fixed-ratio unit completed after 30 minutes elapsed produced the stimulus paired with either cocaine injection or food presentation. Generally, short pauses followed by high rates of responding were maintained within the fixed-ratio units, and responding was positively accelerated over the 30-minute interval. Under another schedule, each completion of a 3-minute fixed-interval unit produced the brief stimulus; completion of the 10th fixed-interval unit produced the stimulus paired with either cocaine injection or food presentation. Generally, short pauses followed by high rates of responding were maintained within the fixed-ratio units, and responding was positively accelerated over the 30-minute interval. Under another schedule, each completion of a 3-minute fixed-interval unit produced the brief stimulus; completion of the 10th fixed-interval unit produced the stimulus paired with either cocaine injection or food presentation. Rates of responding increased within the fixed-interval units, and to a greater extent over the entire 10 fixed-interval units. Patterns of responding depended more on the schedule of reinforcement than on whether cocaine or food maintained responding. Omitting the brief stimuli following all but the last fixed-ratio or fixed-interval units decreased average rates and altered the patterns of responding. Substituting a visual stimulus that was never paired with cocaine or food following all but the last fixed-ratio or fixed-interval units decreased response rates to a lesser extent and did not substantially alter patterns of responding. When the duration of the paired stimulus was varied from .3 to 30.0 seconds, the highest response rates occurred at intermediate durations (1.0 to 10.0 seconds). The manner in which the stimulus changes affected performances depended more on the schedule of reinforcement than on whether cocaine injection or food presentation maintained responding.     

Effects of chlorpromazine on fixed-ratio responding: modification by fixed-interval discriminative stimuli.

Effects of chlorpromazine (1 to 100 mg/kg) were assessed on two pigeons' responding under various modifications of a multiple schedule of food delivery. During a fixed-interval component, the first response after 5 min produced food; during the subsequent, fixed-ratio component, the 30th response produced food. Modifications of the schedule entailed changes in stimulus conditions imposed during the fixed-ratio component that did not systematically alter characteristics of performance under non-drug conditions. In the first phase of the experiment, distinctive visual stimuli were correlated with each schedule component (conventional multiple schedule); chlorpromazine produced small decreases in fixed-ratio responding (20% at 30 mg/kg). When each response during the fixed-ratio component produced the stimulus correlated with the fixed-interval schedule (fixed-interval discriminative stimulus) for 1.2 s, effects of chlorpromazine were not different from those under the conventional multiple schedule. Chlorpromazine produced greater decreases in fixed-ratio responding (55% at 30 mg/kg) when either the first response of each fixed ratio changed the stimulus correlated with the fixed-ratio schedule to the fixed-interval discriminative stimulus for the remainder of the fixed-ratio component, or when the fixed-interval discriminative stimulus was presented independently of responding according to a matched temporal sequence. When the fixed-interval discriminative stimulus was present continuously during the fixed-ratio component (mixed schedule), chlorpromazine produced even more substantial decreases in fixed-ratio responding (greater than 80% at 30 mg/kg). Effects of chlorpromazine on fixed-interval responding were also modified by the schedules of fixed-interval discriminative stimulus presentation. The effects of chlorpromazine were a joint function of the stimuli prevailing during the multiple schedule and the degree to which responding influenced these stimuli.     

Conjunctive schedules of reinforcement: III. A fixed-interval adjusting fixed-ratio schedule

Key pecking of three pigeons was studied under a conjunctive schedule that specified both a fixed-interval and an adjusting fixed-ratio requirement. The fixed-interval schedule was 6 min for one pigeon and 3 min for the other two. The size of the ratio requirement was determined within each cycle of the fixed interval by the duration of the pause before responding began. The fixed-ratio value was at maximum at the start of each fixed interval and decreased linearly until the first response occurred (adjusting fixed-ratio schedule). A peck produced food when the number of responses remaining on the fixed-ratio schedule was completed and when the fixed interval had elapsed. If no response occurred during the interval, the fixed-ratio requirement decreased to one and a single response after the interval elapsed produced food. The initial value of the adjusting fixed-ratio schedule was studied over a range of 0 to 900. Increases in the adjusting fixed-ratio schedule to about 300 responses increased both pause duration and running response rate and also modified the pattern of responding from that obtained under the fixed-interval schedule. Higher values of the adjusting fixed ratio generally decreased pause duration and running response rate and also disrupted responding. Interreinforcement time under the conjunctive schedule was increased substantially when the adjusting fixed-ratio size exceeded 300 responses.     

Alternative fixed-ratio fixed-interval schedules of reinforcement

Five rats were trained under alternative fixed-ratio fixed-interval schedules, in which food reinforcement was provided for the completion of either a fixed-ratio or a fixed-interval requirement, whichever was met first. Overall response rate and running rate (the rate of responding after the postreinforcement pause) decreased for all subjects as the fixed-ratio value increased. As the proportion of reinforcements obtained from the fixed-ratio component increased and the alternative schedule approached a simple fixed ratio, overall response rate and running rate both increased; conversely, as the proportion of reinforcements obtained from the fixed-interval component increased and the alternative schedule approached a simple fixed interval, response rates decreased. Postreinforcement pause length increased linearly as the average time between reinforcements increased, regardless of the schedule parameters. A break-run pattern of responding was predominant at low- and medium-valued fixed ratios. All subjects displayed at least occasional positively accelerated responding within interreinforcement intervals at higher fixed-ratio values.     

The effects of reinforcement frequency and response requirements on the maintenance of behavior.

Six rats responded under fixed-interval and tandem fixed-interval fixed-ratio schedules of food reinforcement. Basic fixed-interval schedules alternated over experimental conditions with tandem fixed-interval fixed-ratio schedules with the same fixed-interval value. Fixed-interval length was varied within subjects over pairs of experimental conditions; the ratio requirement of the tandem schedules was varied across subjects. For both subjects with a ratio requirement of 10, overall response rates and running response rates typically were higher under the tandem schedules than under the corresponding basic fixed-interval schedules. For all subjects with ratio requirements of 30 or 60, overall response rates and running response rates were higher under the tandem schedules than under the corresponding basic fixed-interval schedules only with relatively short fixed intervals. At longer fixed intervals, higher overall response rates and running rates were maintained by the basic fixed-interval schedules than by the tandem schedules. These findings support Zeiler and Buchman's (1979) reinforcement-theory account of response strength as an increasing monotonic function of both the response requirement and reinforcement frequency. Small response requirements added in tandem to fixed-interval schedules have little effect on reinforcement frequency and so their net effect is to enhance responding. Larger response requirements reduce reinforcement frequency more substantially; therefore their net effect depends on the length of the fixed interval, which limits overall reinforcement frequency. At the longest fixed intervals studied in the present experiment, reinforcement frequency under the tandem schedules was sufficiently low that responding weakened or ceased altogether.     

A comparison of ratio and interval reinforcement schedules with comparable interreinforcement times

Pigeons were trained to peck keys on fixed-ratio and fixed-interval schedules of food reinforcement. Both schedules produced a pattern of behavior characterized as pause and run, but the relation of pausing to time between reinforcers differed for the two schedules even when mean time between reinforcers was the same. Pausing in the fixed ratio occupied less of the time between reinforcers for shorter interreinforcer times. For two of three birds, the relation was reversed at longer interreinforcer times. As an interreinforcer time elapsed, there was an increasing tendency to return to responding for the fixed interval, but a roughly constant tendency to return to responding for the fixed-ratio schedule. In Experiment 1 these observations were made for both single-reinforcement schedules and multiple schedules of fixed-ratio and fixed-interval reinforcement. In Experiment 2 the observations were extended to a comparison of fixed-ratio versus variable-interval reinforcement schedules, where the distribution of interreinforcement times in the variable interval approximated that for the fixed ratio.     

Changing the response unit from a single peck to a fixed number of pecks in fixed-interval schedules

Each of three pigeons was studied first under a standard fixed-interval schedule. With the fixed interval held constant, the schedule was changed to a second-order schedule in which the response unit was the behavior on a small fixed-ratio schedule (first a fixed-ratio 10 and then a fixed-ratio 20 schedule). That is, every completion of the fixed-ratio schedule produced a 0.7-sec darkening of the key and reset the response count to zero for the next ratio. The first fixed-ratio completed after the fixed-interval schedule elapsed produced the 0.7-sec blackout followed immediately by food. These manipulations were carried out under two different fixed-interval durations for each bird ranging from 3 min to 12 min. The standard fixed-interval schedules produced the typical pause after reinforcement followed by responding at a moderate rate until the next reinforcement. The second-order schedules also engendered a pause after reinforcement, but responding occurred in bursts separated by brief pauses after each blackout. For a particular fixed-interval duration, post-reinforcement pauses increased slightly as the number of pecks in the response unit increased despite large differences in the rate and pattern of key pecking. Post-reinforcement pause increased with the fixed-interval duration under all response units. These data confirm that the allocation of time between pausing and responding is relatively independent of the rate and topography of responding after the pause.     

Effects of concurrent response-independent reinforcement on fixed-interval schedule performance

In three experiments, behavior maintained by fixed-interval schedules changed when response-independent reinforcement was delivered concurrently according to fixed- or variable-time schedules. In Experiment I, a pattern of positively accelerated responding during fixed interval was changed to a linear pattern when response-independent reinforcement occurred under a variable-time schedule. Overall response rates (total responses/total time) decreased as the frequency of response-independent reinforcement increased. Experiment II showed that the response-rate changes in the first experiment were controlled by the response-reinforcer relation, but the changes in patterns of responding were similar whether concurrently available reinforcement at varying times was response-dependent or response-independent. In the final experiment, the addition of response-independent reinforcement at fixed times to a fixed-interval schedule resulted in changes in both local and overall response rates and in the occurrence of positively accelerated responding between reinforcements. These results suggest that the temporal distribution of reinforcers determines response patterns and that both the response-reinforcement dependency and the schedule of reinforcement determine overall response rates during concurrently scheduled response-dependent and response-independent reinforcement.     

Neurochemical changes correlated with behavior maintained under fixed-interval and fixed-ratio schedules of reinforcement.

Key pecking of 4 pigeons was maintained under a multiple 3-min fixed-interval, 30-response fixed-ratio schedule of food presentation. Only one schedule was in effect during an experimental session, and each was correlated with a different keylight stimulus and location (left vs. right). The different schedule components alternated across days or weeks. Cerebrospinal fluid was collected from chronically implanted intracerebroventricular cannulae following sessions with the different schedules, as well as following sessions in which reinforcement was withheld (extinction), when response-independent food was delivered, and when the experimental chamber was dark and there were no scheduled events. Metabolites of the neurotransmitters serotonin, norepinephrine, and dopamine were assayed in cerebrospinal fluid using high-performance liquid chromatography with electrochemical detection. Compared to the fixed-ratio condition, responding maintained under the fixed-interval schedule resulted in consistently higher levels of the serotonin metabolite 5-hydroxyindoleacetic acid and of the dopamine metabolite homovanillic acid in all pigeons. Levels of 3-methoxy-4-hydroxyphenylethylene glycol, a metabolite of norepinephrine, and dihydroxyphenylacetic acid, another dopamine metabolite, were also higher in 3 of the 4 pigeons following exposure to the fixed-interval schedules when compared to levels of these metabolites after exposure to the fixed-ratio schedule. Extinction of fixed-ratio responding resulted in large increases in 5-hydroxyindoleacetic acid compared to levels of this metabolite under the fixed-ratio schedule, whereas this serotonin metabolite decreased during extinction of responding under the fixed-interval schedule. Control procedures suggested that the neurochemical changes were not related to the rate of responding but were a function of the specific experimental conditions. Distinctive neurochemical changes that accompany schedule-controlled responding show the sensitivity of the neurochemical environment to behavioral contingencies and demonstrate further the profound impact that such contingencies have on biobehavioral processes.     

Concurrent fixed-interval variable-ratio schedules and the matching relation

Five rats responded under concurrent fixed-interval variable-ratio schedules of food reinforcement. Fixed-interval values ranged from 50-seconds to 300-seconds and variable-ratio values ranged from 30 to 360; a five-second changeover delay was in effect throughout the experiment. The relations between reinforcement ratios obtained from the two schedules and the ratios of responses and time spent on the schedules were described by Baum's (1974) generalized matching equation. All subjects undermatched both response and time ratios to reinforcement ratios, and all subjects displayed systematic bias in favor of the variable-ratio schedules. Response ratios undermatched reinforcement ratios less than did time ratios, but response ratios produced greater bias than did time ratios for every subject and for the group as a whole. Local rates of responding were generally higher on the variable-ratio than on the fixed-interval schedules. When responding was maintained by both schedules, a period of no responding on either schedule immediately after fixed-interval reinforcement typically was followed by high-rate responding on the variable-ratio schedule. At short fixed-interval values, when a changeover to the fixed-interval schedule was made, responding usually continued until fixed-interval reinforcement was obtained; at longer values, a changeover back to the variable-ratio schedule usually occurred when fixed-interval reinforcement was not forthcoming within a few seconds, and responding then alternated between the two schedules every few seconds until fixed-interval reinforcement finally was obtained.     

Pentobarbital and d-amphetamine effects on concurrent performances.

The effects of pentobarbital and d-amphetamine were studied in pigeons responding under several concurrent fixed-ratio variable-interval and concurrent fixed-ratio fixed-interval schedules of food presentation. Drug effects were compared with different fixed ratios, fixed and variable intervals, changeover delays, and with the schedules operating singly. Doses of d-amphetamine that increased or did not affect responding under the interval schedules decreased responding under the fixed-ratio schedule, whereas doses of pentobarbital that increased responding under the fixed-ratio schedule decreased or eliminated responding under the interval schedules. These effects depended both on the schedule of food delivery and the parameters of schedules arranged concurrently. Pentobarbital increased responding under the fixed-ratio schedule with 4-minute and 10-minute interval schedules arranged concurrently, but not with 1.5-minute schedules. d-Amphetamine decreased concurrent ratio and interval responding with the 1.5-minute interval schedules, but either increased or did not affect responding with the longer intervals. Changes in the parameter of one schedule altered responding controlled by that schedule and also other concurrent performances. As a consequence, the effects of drugs on each behavior were altered.     

Response requirements as constraints on output

Two experiments studied how added response requirements affected fixed-interval schedule performance. Experiment 1 involved tandem fixed-interval fixed-ratio schedules, and Experiment 2 studied conjunctive fixed-interval fixed-ratio schedules. In both, pigeons' output, defined as overall response rate or as responses during the interval, first increased and then decreased as the ratio was raised. With small ratio requirements, the frequency of reinforcement in time either did not change or decreased slightly. With progressively larger ratios, reinforcement frequency decreased consistently. Alternative explanations were discussed. The first, a reinforcement theory account, was that response strength is an increasing monotonic function of both the response requirement and reinforcement frequency, and the bitonic output function represents interacting effects. Increases in the response requirement accompanied by small changes in reinforcement frequency enhance output, but further increases result in large enough decrements in reinforcement frequency so that output is lowered. The second explanation does not view reinforcement as a basic process but, instead, derives from concepts of economics and conservation. Organisms allocate their behavior among alternatives so as to maximize value, where value is a function of the responses that can occur in a given situation under the set of restrictions imposed by particular schedules. One form of this theory explicitly predicts that output is a bitonic function of ratio requirements in simple ratio schedules. However, it was not clear that this model could explain the present effects involving joint ratio and interval schedule restrictions.     

Tests of behavior momentum in simple and multiple schedules with rats and pigeons.

Four experiments examined the relationship between rate of reinforcement and resistance to change in rats' and pigeons' responses under simple and multiple schedules of reinforcement. In Experiment 1, 28 rats responded under either simple fixed-ratio, variable-ratio, fixed-interval, or variable-interval schedules; in Experiment 2, 3 pigeons responded under simple fixed-ratio schedules. Under each schedule, rate of reinforcement varied across four successive conditions. In Experiment 3, 14 rats responded under either a multiple fixed-ratio schedule or a multiple fixed-interval schedule, each with two components that differed in rate of reinforcement. In Experiment 4, 7 pigeons responded under either a multiple fixed-ratio or a multiple fixed-interval schedule, each with three components that also differed in rate of reinforcement. Under each condition of each experiment, resistance to change was studied by measuring schedule-controlled performance under conditions with prefeeding, response-independent food during the schedule or during timeouts that separated components of the multiple schedules, and by measuring behavior under extinction. There were no consistent differences between rats and pigeons. There was no direct relationship between rates of reinforcement and resistance to change when rates of reinforcement varied across successive conditions in the simple schedules. By comparison, in the multiple schedules there was a direct relationship between rates of reinforcement and resistance to change during most tests of resistance to change. The major exception was delivering response-independent food during the schedule; this disrupted responding, but there was no direct relationship between rates of reinforcement and resistance to change in simple- or multiple-schedule contexts. The data suggest that rate of reinforcement determines resistance to change in multiple schedules, but that this relationship does not hold under simple schedules.     

Reinforcement by an imprinting stimulus versus water on simple schedules in ducklings

Ducklings (5 to 28 days old) were trained to peck a pole on fixed-ratio, fixed-interval, and multiple schedules using brief presentation of an imprinting stimulus as the response-contingent event. Other ducklings of the same age were trained similarly except that reinforcement consisted of access to water. With water reinforcement the typical fixed-ratio (“break-run”), fixed-interval (“scallop”), and multiple schedule response patterns were readily established and consistently maintained. With the imprinting stimulus these schedule effects were inconsistent in some subjects and virtually nonexistent in others, despite extended training. Schedule control with the imprinting stimulus was not improved by the use of a reinforcement signaling procedure which enhances responding reinforced by electrical brain stimulation on intermittent schedules. However, the overall rates of responding and the extinction functions generated after reinforcement with water versus the imprinting stimulus were comparable. These findings imply that control by temporal and discriminative stimuli may be relatively weak when a young organism's behavior is reinforced by presentation of an imprinting stimulus.     

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.     

INFLUENCES ON COCAINE TOLERANCE ASSESSED UNDER A MULTIPLE CONJUNCTIVE SCHEDULE OF REINFORCEMENT

Under multiple schedules of reinforcement, previous research has generally observed tolerance to the rate‐decreasing effects of cocaine that has been dependent on schedule‐parameter size in the context of fixed‐ratio (FR) schedules, but not under the context of fixed‐interval (FI) schedules of reinforcement. The current experiment examined the effects of cocaine on key‐pecking responses of White Carneau pigeons maintained under a three‐component multiple conjunctive FI (10 s, 30 s, & 120 s) FR (5 responses) schedule of food presentation. Dose‐effect curves representing the effects of presession cocaine on responding were assessed in the context of (1) acute administration of cocaine (2) chronic administration of cocaine and (3) daily administration of saline. Chronic administration of cocaine generally resulted in tolerance to the response‐rate decreasing effects of cocaine, and that tolerance was generally independent of relative FI value, as measured by changes in ED50 values. Daily administration of saline decreased ED50 values to those observed when cocaine was administered acutely. The results show that adding a FR requirement to FI schedules is not sufficient to produce schedule‐parameter‐specific tolerance. Tolerance to cocaine was generally independent of FI‐parameter under the present conjunctive schedules, indicating that a ratio requirement, per se, is not sufficient for tolerance to be dependent on FI parameter.     

Schedule-induced defecation by rats during ratio and interval schedules of food reinforcement.

Lever pressing in rats was maintained by continuous and intermittent schedules of food while defecation was monitored. In Experiment 1, reinforcement densities were matched across variable-ratio and variable-interval schedules for three pairs of rats. Defecation occurred in all 3 rats on the variable-ratio schedule and in all 3 rats on the yoked variable-interval schedule. In Experiment 2, fixed-ratio and fixed-interval schedules with similar reinforcement densities maintained lever pressing. Defecation occurred in 3 of 4 rats on the fixed-ratio schedule and in 4 of 4 rats on the fixed-interval schedule. Almost no defecation occurred during continuous reinforcement in either experiment. These results demonstrate that defecation may occur during both ratio and interval schedules and that the inter-reinforcement interval is more important than the behavioral requirements of the schedule in generating schedule-induced defecation.     

Schedule control of the vocal behavior of Cebus monkeys

The vocal behavior of three Cebus monkeys was maintained by fixed-ratio schedules of response dependent reinforcement at values between fixed-ratio 1 and fixed-ratio 15. In one monkey that was exposed to variable-interval, fixed-interval, and conjunctive fixed-ratio fixed-interval schedules of reinforcement, vocal responding occurred at a low rate, but schedule-appropriate patterns were maintained. The rates and patterns of responding engendered indicated that the vocal operant can be brought under schedule control in the monkey by the use of response-dependent reinforcement.