Conditioned suppression by a stimulus associated with nalorphine in morphine-dependent monkeys

Three rhesus monkeys, physically dependent on morphine, were trained to press a lever for food on a fixed ratio of 10 responses. A tone, initially a neutral stimulus, was aperiodically presented every third or fourth session, 5 min before and after the intravenous injection of nalorphine, a morphine antagonist which produces an immediate withdrawal syndrome in morphine-dependent monkeys. After several sessions, conditioned suppression of food-lever response rate was observed. Conditioned bradycardia, emesis, and excessive salivation also occurred. In 40 to 45 sessions the conditioned suppression of food-lever response rate and the conditioned autonomic changes were extinguished by presenting pairings of a tone and saline injection. The monkeys were then reconditioned by presenting the tone aperiodically, every third or fourth session, 5 min before and after the intravenous injection of nalorphine. Results were similar to the initial conditioning sessions. Two rhesus monkeys not dependent on morphine were stabilized on a food schedule similar to that used for the first three monkeys. These monkeys showed no change in food-lever response rate during or after nalorphine injections.     

Conditioned nalorphine-induced abstinence changes: persistence in post morphine-dependent monkeys

Every tenth lever-press of three morphine-dependent rhesus monkeys was reinforced with food. A red light, initially a neutral stimulus, was presented every third or fourth session for 5 min before and 5 min after an intravenous injection of nalorphine, a morphine antagonist that produces an immediate abstinence syndrome in morphine-dependent monkeys. After several pairings, conditioned suppression of lever pressing, heart-rate decrease, vomiting, and excessive salivation were observed during the red-light period before nalorphine injection. No conditioned electrocardiogram, respiration or temperature changes occurred. After 10 red light-nalorphine pairings, morphine administration was completely discontinued and monkeys were then tested monthly for persistence of the conditioned responses. The red light paired with saline injection continued to suppress lever pressing and to produce heart-rate decreases after 60 to 120 days of complete abstinence from morphine. Subsequently, daily presentations of the red light-saline injection complex rapidly extinguished these conditioned responses. Nevertheless, they could be rapidly reinstated by additional nalorphine injections.     

Role of conditioned reinforcers in the initiation,maintenance and extinction of drug-seeking behavior

The development of a secondary reinforcer as a result of associating a neutral stimulus (buzzer) with intravenous (IV) doses of morphine was studied in rats. Secondary reinforcement developed in the absence of physical dependence and followed the association of the stimulus with either response-contingent or non-contingent injections of morphine. Strength of the conditioned reinforcer, measured in terms of responding on a lever for the stimulus plus infusion of saline solution, was proportional to the unit dosage of morphine employed in pairings of buzzer and drug. When extinction of the lever-press response for IV morphine was conducted (by substituting saline for morphine solution) in the absence of the conditioned reinforcing stimulus, it was seen later that the stimulus could still elicit lever responses, until it too had been present for a sufficient interval of non-reinforced responding. Similarly, extinction of the response for morphine by blocking its action with naloxone in the absence of the stimulus did not eliminate the conditioned reinforcement. Another study showed that a passive, subcutaneous (SC) dose of morphine served to maintain lever-pressing on a contingency of buzzer plus sahne infusion. Furthermore, the stimuli resulting from the presence of morphine (after a SC injection) were able to reinstate the lever-responding with only the buzzer-saline contingency when such responses had previously been extinguished. Moreover, it was shown thatd-amphetamine could restore responding under the same conditions, and that morphine could also do so for rats in which the primary reinforcer had beend-amphetamine. It is suggested that animal data such as these show that procedures designed for the elimination of human drug-taking behavior must take into account secondary reinforcers as well as the primary reinforcer(s).     

Acquisition of cocaine self-administration with unsignaled delayed reinforcement in rhesus monkeys

Six experimentally naive rhesus monkeys produced 0.01 mg/kg/infusion cocaine by lever pressing under a tandem fixed-ratio 1 differential-reinforcement-of-other-behavior schedule. One lever press initiated an unsignaled 15- or 30-s delay culminating in cocaine delivery. Each press made during the delay reset the delay interval. With two exceptions, responding was acquired and maintained at higher rates than responding on a second (inoperative) lever. For the exceptions, a cancellation contingency was arranged in which each formerly inoperative-lever response reset the tandem schedule. This manipulation reduced presses on the inoperative lever. Subsequently, the consequences of responding on the two levers were reversed, and the monkeys again responded at higher rates on the operative lever. As a comparison, 3 additional experimentally naive monkeys received response-independent cocaine deliveries. Although lever pressing was observed, it extinguished and was subsequently reestablished under the tandem schedule. The results suggest that although response-reinforcer contiguity is not required for cocaine to acquire reinforcing functions, a response-reinforcer relation appears necessary.     

The conditioned reinforcement of repeated acquisition

Three monkeys were trained to emit a chain of three responses on three separate levers in a set of six levers to obtain food. The chain producing food (correct chain) was changed each day. During a trial, a press on any lever produced a feedback stimulus; a press on a correct lever produced an additional distinctive stimulus; the third correct press produced a food pellet. Test sessions in which either the food or the distinctive stimuli were removed were interspersed with baseline sessions. In tests without food presentations, the subjects acquired the correct chain rapidly, with a level of accuracy comparable to baseline. Removing the distintive stimuli for either the first or second member of the correct chain greatly retarded acquisition of that member of the chain. Removing all distinctive stimuli often reduced accuracy throughout the chain to chance level, even though food was presented following each correct chain. These results were interpreted as evidence that the distinctive stimuli presented after correct responses functioned as conditioned reinforcers. Reductions in accuracy following an omitted distinctive stimulus indicated that they were also discriminative stimuli for correct responding in their presence.     

Behavior simultaneously maintained by both presentation and termination of noxious stimuli

Lever pressing by two squirrel monkeys was maintained under a 3-minute variable-interval schedule of response-produced electric-shock presentation. At the same time, responding on a second lever was maintained under a 3-minute fixed-interval schedule of termination of the shock-presentation schedule and shock-correlated stimuli. Under the termination schedule, the first response after a 3-minute period produced a 1-minute timeout, during which no events occurred and responding had no scheduled consequence. Relatively high and constant rates of responding were maintained on the lever where responding produced shock. Lower rates and positively accelerated patterns of responding occurred on the lever where responding terminated the shock schedule. Thus, responding was simultaneously maintained by presentation of an event and by termination of a stimulus associated with that event. Rates and patterns of responding on each lever were reversed when the schedules arranged on each lever were reversed on two occasions. When shock intensity was increased from 0 to 10 mA, responding maintained both by presentation of shock and by termination of the shock schedule increased, but responding maintained by shock presentation increased to a greater extent. Positive and negative reinforcement, usually regarded as separate behavioral processes involving different events, can coexist when behavior is controlled by different contingencies involving the same event.     

The generality of selective observing

Four rats obtained food pellets by poking a key and 5-s presentations of the discriminative stimuli by pressing a lever. Every 1 or 2 min, the prevailing schedule of reinforcement for key poking alternated between rich (either variable-interval [VI] 30 s or VI 60 s) and lean (either VI 240 s, VI 480 s, or extinction) components. While the key was dark (mixed-schedule stimulus), no exteroceptive stimulus indicated the prevailing schedule. A lever press (i.e., an observing response), however, illuminated the key for 5 s with either a steady light (S+), signaling the rich reinforcement schedule, or a blinking light (S-), signaling the lean reinforcement schedule. One goal was to determine whether rats would engage in selective observing (i.e., a pattern of responding that maintains contact with S+ and decreases contact with S-). Such a pattern was found, in that a 5-s presentation of S+ was followed relatively quickly by another observing response (which likely produced another 5-s period of S+), whereas exposure to S- resulted in extended breaks from observing. Additional conditions demonstrated that the rate of observing remained high when lever presses were effective only when the rich reinforcement schedule was in effect (S+ only condition), but decreased to a low level when lever presses were effective only during the lean reinforcement component (S- only condition) or when lever presses had no effect (in removing the mixed stimulus or presenting the multiple-schedule stimuli). These findings are consistent with relativistic conceptualizations of conditioned reinforcement and extend the generality of selective observing to procedures in which the experimenter controls the duration of stimulus presentations, the schedule components both offer intermittent food reinforcement, and rats serve as subjects.     

Reversibility of single-incentive selective associations.

Rats were trained to press a lever in the presence of a tone-light compound stimulus and not to press in its absence. In each of two experiments, schedules were designed to make the compound a conditioned punisher for one group and a conditioned reinforcer for the other. In Experiment 1, one group's responding produced food in the presence of the compound but not in its absence. The other group's responding terminated the compound stimulus, and food was presented only in its absence. When tone and light were later presented separately, light controlled more responding than did tone in the former group, but tone gained substantial control in the latter. The same effects were also observed within subjects when the training schedules were switched over groups. In Experiment 2, two groups avoided shock in the presence of the compound stimulus. In the absence of the compound, one group was not shocked, and the other received both response-independent and response-produced shock. When tone and light were presented separately, the former group's responding was mainly controlled by tone, but the latter group's responding was almost exclusively controlled by light. These effects were also observed within subjects when the training schedules were switched over groups. Thus, these single-incentive selective association effects (appetitive in Experiment 1 and aversive in Experiment 2) were completely reversible. The schedules in which the compound should have been a conditioned reinforcer consistently produced visual control, and auditory control increased when the compound should have become a conditioned punisher. Currently accepted accounts of selective associations based on affinities between shock and auditory stimuli and between food and visual stimuli (i.e., stimulus-reinforcer interactions) do not adequately address these results. The contingencies of reinforcement most recently associated with the compound and with its absence, rather than the nature of the reinforcer, determined whether auditory or visual stimulus control developed.     

Positive reinforcement and suppression from the same occurrence of the unconditioned stimulus in a positive conditioned suppression procedure

Responding of rats was maintained on a variable-interval schedule of food reinforcement. The same response also produced a blinking light followed by electrical brain stimulation according to a fixed-interval schedule. This conjoint schedule produced two behavioral changes. First, instead of a steady rate of responding throughout the session, which would be characteristic of the variable interval food schedule alone, responding between occurrences of the light-brain stimulation pairings became positively accelerated and thus was more characteristic of the fixed-interval schedule of these pairings. Second, food responding was suppressed during the light that preceded brain stimulation. These results indicate that positive reinforcement and suppression resulted from the same occurrence of the light-brain stimulation combination. This finding suggests that stimuli such as conditioned reinforcers that precede an unconditioned reinforcer may have a suppressive effect upon responding in their presence that is being maintained by another reinforcer.     

Observing behavior in squirrel monkeys under a multiple schedule of reinforcement availability

Observing behavior of two squirrel monkeys was examined under a multiple schedule of four components. Lever (observing) responses produced either a stimulus indicating the availability of food or another stimulus indicating food was not available. Key responses in the presence of the food-available stimulus produced food on a continuous reinforcement schedule. In the absence of food-available stimuli, responding on the key had no scheduled consequences. Observing responses produced food-available stimuli according to three different random-interval schedules with mean interstimulus availability times of 1, 2, and 4 min. In the fourth component of the multiple schedule (observing extinction) food-available stimuli never occurred. Each component of the schedule was correlated with a distinctive auditory stimulus. Observing rates decreased with decreasing frequency of the food-available stimulus. Observing rates during extinction continued decreasing when the brief stimulus indicating food unavailability was no longer produced by lever pressing. When the brief stimulus was reinstated response rates increased abruptly.     

Drug-behavior interaction history: modification of the effects of morphine on punished behavior.

Squirrel monkeys were trained to respond under a multiple fixed-interval, fixed-interval schedule in which the first response after 5 min terminated a visual stimulus in the presence of which electric shocks could occur. During one component of the schedule, correlated with one color of stimulus lights, every 30th response also produced electric shock; responding was suppressed during this component to approximately 10 to 12% of that occurring in the alternate component in which responding was not punished. In contrast to previous research, morphine (0.03 to 1.0 mg/kg) increased punished responding. Unpunished responding, however, was either not affected or decreased at doses of morphine that increased punished responding. Increases in rate of punished responding also occurred when the single-schedule punishment condition was studied alone in these animals. Subsequent experimentation, which systematically analyzed the development of the rate-enhancing effects of morphine on punished responding, involved the study of drug effects in additional monkeys trained initially under a single-schedule punishment condition. The effects of morphine on punished responding were studied before, after, and then during exposure to the multiple schedule that included a component in which responding was not punished. Increases in response rate with morphine did not occur until it was administered during exposure to the multiple schedule that included a component in which responding was not punished. As with the other monkeys, once the rate increases in punished responding occurred under the multiple schedule, these effects of morphine persisted, even when the multiple schedule was removed.(ABSTRACT TRUNCATED AT 250 WORDS)     

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).     

Observing responses in rats: Support for the secondary reinforcement hypothesis

Rats' lever presses on a retractable lever earned brief presentations of discriminative stimuli signalling periods in which responding on an alternative lever was either non-reinforced (extinction) or reinforced on a random ratio schedule. The predictions of two theoretical accounts of this behaviour were tested by studying the effects of omitting either the stimulus signalling the reinforced or that signalling the non-reinforced schedule component. Under these conditions rats' behaviour is determined by the conditioned, affective properties of the stimuli rather than by their purely informational properties.     

Concurrent performances: reinforcement by different doses of intravenous cocaine in rhesus monkeys

Different doses of intravenous cocaine reinforced the lever pressing of rhesus monkeys under two-lever concurrent or concurrent-chain schedules. Under the concurrent procedure, responding produced drug reinforcers arranged according to independent variable-interval 1-min schedules. Under the concurrent-chain procedure, responding in the variable-interval link led to one of two mutually exclusive, equal-valued, fixed-ratio links; completion of the ratio produced a drug reinforcer. Under both procedures, responding on one lever produced a constant dose of 0.05 or 0.1 mg/kg/injection, while on the other lever, dose was systematically varied within a range of 0.013 to 0.8 mg/kg/injection. Preference, indicated by relative response frequency on the variable-dose lever during the variable-interval link, was always for the larger of the doses. Relative response frequencies on the variable-dose lever roughly matched relative drug intake (mg/kg of drug obtained on variable lever divided by mg/kg of drug obtained on both levers). For many dose comparisons, responding occurred and reinforcers were obtained almost exclusively on the preferred lever. Overall variable-interval rates generally were lower than with other reinforcers, and these low rates, under the experimental conditions, may have occasioned the exclusive preferences.     

Fixed-interval responding under second-order schedules of food presentation or cocaine injection.

Squirrel monkeys operated a key under second-order schedules in which every tenth completion of a 5-minute fixed interval resulted in either presentation of food or intravenous injection of cocaine. When a 2-second light was presented at the completion of the component fixed-interval schedules, positively accelerated responding developed and was maintained in each component. Over a tenfold range of doses of cocaine(30 to 300 microgram/kg/injection) and amounts of food (0.75 to 7.5 g/presentation); the second-order schedule of cocaine injection maintained higher average rates of responding than the second-order schedule of food presentation. Substituting saline for cocaine or eliminating food presentation decreased average rates of responding. When no stimulus change occurred at the completion of the first nine component fixed-interval schedules, but the 2-second light and food presentation or cocaine injection still occurred after the tenth component, only low and relatively constant rates of responding were maintained in each component. Patterns of responding characteristic of 5-minute fixed-interval schedules were maintained by the 2-second light paired with either cocaine injection or food presentation, though the maximum frequency of cocaine injection or food presentation was less than once per 50 minutes.     

The Rescorla-Wagner model: losses in associative strength in compound conditioned stimuli

This series of experiments demonstrated that compound conditioned stimuli (CSs) highly conditioned in isolation lose conditioned response strength when compound-CS-unconditioned stimulus (US) pairings are given. This loss in conditioned responding was a positive function of the number of compound-CS-US pairings and was greater for the more salient stimulus. Finally, if a previously neutral stimulus was compounded with two previously conditioned cues, the neutral stimulus could acquire conditioned inhibitory properties with only compound-CS-US pairings. These results provide support for some aspects of the Rescorla-Wagner model.     

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.     

Conditioned suppression of drl responding: Effect of ucs intensity, schedule parameter, and schedule context

In Experiment I, groups of rats were trained to press a lever for food reinforcement on differential reinforcement of low rate (DRL) schedules which differed in parameter value. A stimulus which terminated with either a 0.5-mA or 2.0-mA electric shock was then superimposed upon each DRL baseline. In general, the magnitude of conditioned suppression was an inverse function of DRL schedule parameter and a direct function of shock intensity. Experiment II demonstrated that the rate of responding maintained by the DRL component of a multiple DRL-extinction schedule decreased during a stimulus preceding a 0.5-mA shock, whereas the rate of responding maintained by the DRL component of a multiple DRL-variable interval schedule showed little change or increased slightly during a stimulus preceding a 0.5-mA shock.     

Behavior of rats under fixed consecutive number schedules: effects of drugs of abuse.

Four rats responded under a simple fixed consecutive number schedule in which eight or more consecutive responses on the run lever, followed by a single response on the reinforcement lever, produced the food reinforcer. Under this simple schedule, dose-response curves were determined for diazepam, morphine, pentobarbital, and phencyclidine. The rats were then trained to respond under a multiple fixed consecutive number schedule in which a discriminative stimulus signaled when the response requirement on the run lever had been completed in one of the two fixed consecutive number component schedules. Under control conditions, the percentage of reinforced runs under the multiple-schedule component with the discriminative stimulus added was much higher than the percentage of reinforced runs under the multiple-schedule component without the discriminative stimulus. All of the drugs decreased the percentage of reinforced runs under each of the fixed consecutive number schedules by increasing the conditional probability of short run lengths. This effect was most consistently produced by morphine. The drugs produced few differences in responding between the multiple fixed consecutive number components. Responding under the simple fixed consecutive number schedule, however, was affected at lower doses of the drugs than was responding under the same fixed consecutive number schedule when it was a component of the multiple schedule. This result may be due to the difference in schedule context or, perhaps, to the order of the experiments.     

Conditioned suppression and conditioned enhancement with the same positive UCS: an effect of CS duration

Previous experiments have shown that positively reinforced operant responding is suppressed during a conditioned stimulus terminated with an electric shock (conditioned suppression). In the present experiment, the conditioned stimulus was terminated with a positive unconditioned stimulus, and it was found that the duration of the conditioned stimulus was a key factor in determining whether response suppression or response enhancement was observed during the stimulus. The lever-pressing responses of rats were maintained by a variable-interval schedule of food reinforcement. While the rats were pressing the lever, a light was occasionally turned on, its offset coincident with a brief period of access to a sucrose solution. In consecutive blocks of sessions, the light duration was 40 sec, 12 sec, or 120 sec. Results showed that the rate of lever pressing was substantially suppressed during the 12-sec stimulus, slightly suppressed during the 40-sec stimulus, and enhanced during the 120-sec stimulus.