Effects of atropine on the repeated acquisition and performance of response sequences in humans.

The present study assessed a 24-hr time course for the acute effects of intramuscular injections of atropine sulfate (0, 1.5, 3.0, and 6.0 mg/70 kg) in healthy adult humans responding under a two-component multiple schedule of repeated acquisition and performance of response sequences. Subjects resided in an inpatient research ward for the duration of the study. In each component of the multiple schedule, subjects completed a different sequence of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component, the subjects' task was to acquire a new sequence each session. Eight sessions were conducted daily: one immediately before administration of the drug and then 0.5, 1.5, 3.0, 5.0, 7.0, 9.0, and 24.0 hr after administration. In the performance component, the response sequence always remained the same. Overall percentage of errors increased and overall response rates decreased in the acquisition and performance components as an orderly function of drug dose. However, these effects were selective in that behavior in the acquisition component generally was affected at lower doses than in the performance component. When behavior was affected in both the acquisition and performance components, the time courses of effects were similar. Drug effects began at 0.5 or 1.5 hr, reached peak effects between 3.0 and 5.0 hr, and returned to placebo levels between 7.0 and 9.0 hr postdrug in both schedule components. None of the drug doses produced reliable effects the day after drug administration (24-hr postdrug) in either schedule component. The present study provides the first within-subject assessment of the magnitude and duration of the effects of an anticholinergic on repeated acquisition and performance baselines and extends to atropine the selective effects on these two baselines demonstrated previously with other compounds in humans and nonhumans.     

An experimental analysis of the effects of d-amphetamine and cocaine on the acquisition and performance of response chains in monkeys.

In one component of a multiple schedule of food presentation, monkeys acquired a different four-response chain each session by responding sequentially on three keys in the presence of four geometric forms (learning). In the other component, the four-response chain was the same each session (performance). Both d-amphetamine and cocaine, at the higher doses, disrupted the behavior in the learning component; the overall response rate decreased, the overall accuracy was impaired (i.e., percent errors increased), and there was less within-session error reduction. The performance component was generally less sensitive than the learning component to the disruptive effects of both drugs on rate and accuracy. After pre-feeding or during an extended session, the response rate decreased in both components, but accuracy was generally unaffected. When the four discriminative stimuli in both components were removed, the behavior was disrupted to a greater extent in the performance component. The disruptive effects of both drugs on behavior in the learning component were attenuated when the drugs were administered during the session after the response chain had been acquired. It was concluded that the greater sensitivity of the learning component to disruptive drug effects is related to the relatively weak stimulus control and/or the lower rate of reinforcement associated with that component.     

The effects of diazepam and triazolam on repeated acquisition and performance of response sequences with an observing response.

Drugs often disrupt the acquisition of new response sequences at doses that fail to disrupt the performance of a previously acquired response sequence. This selective drug effect may result from differences in the control exerted by the stimuli presented after each response in the acquisition and performance sequences. To examine the function of these stimuli, an observing procedure was incorporated into a multiple schedule of repeated acquisition and performance of response sequences, in which stimulus presentations were contingent upon an observing response. Three experiments were conducted with humans. Experiment 1 compared responding with and without the observing contingency. No difference was found in the overall percentage of errors across the two conditions. Within the observing condition, observing behaviour was maintained in the acquisition component as long as errors occurred, but was not maintained in the performance component. Experiment 2 examined whether a contingency that increased errors also would increase observing in both the acquisition and performance components. Specifically, reinforcer delivery in each component was contingent upon emitting 10 correct responses and one, two, or four errors. Observing responses increased in the acquisition component as the error requirement increased, whereas observing responses in the performance component increased only when the error requirement was four. Experiment 3 assessed the effects of diazepam (0, 7.5, 15, and 30 mg/70 kg, p.o.) and triazolam (0, 0.375, and 0.75 mg/70 kg, p.o.) on repeated acquisition and performance baselines with the observing contingency. Selective drug effects were obtained in this modified procedure; that is, the percentage of errors in the acquisition component increased at doses that failed to affect the percentage of errors in the performance components. Importantly, drug effects were selective, even though observing responses were not emitted in the performance component and, hence, the stimulus presentations did not occur in that component. These findings suggest that alternative explanations for these differential effects are needed; in that regard, a response-unit account of the selective drug effects is discussed.     

Repeated diazepam administration: effects on the acquisition and performance of response chains in humans.

The effects of repeated diazepam administration (80 mg) were assessed across a 12-hr time course with humans responding under a two-component multiple schedule of repeated acquisition and performance of response sequences. Subjects resided in an inpatient clinical research ward for the duration of the study. In each component of the multiple schedule, subjects completed sequences of 10 responses in a predetermined order using three keys of a numeric keypad. In the acquisition component, a new response sequence was to be acquired each session. In the performance component, the response sequence always remained the same. After stable responding was obtained and the effects of the placebo assessed, diazepam was administered for 3 consecutive days. The effects of repeated diazepam administration on overall percentage of errors across the two components of the multiple schedule were selective. In the acquisition component, the first dose of diazepam increased percentage errors with the magnitude of effects decreasing across the second and third days of diazepam administration. In the performance component, the percentage of errors was either minimally affected across all 3 days of diazepam administration or substantively increased on Day 1 with subsequent diazepam administrations having minimal effects. Effects on response rate were not selective. Diazepam decreased rates of responding in both schedule components, with the magnitude of effects decreasing across successive administrations. These results replicate previous findings in humans and nonhumans on the selective effects of diazepam on acquisition versus performance baselines. Also, the results suggest that the selective effects do not result from differences in reinforcement rate. Finally, the present results demonstrate that the selective recovery from repeated drug administration previously demonstrated in nonhumans using a repeated acquisition arrangement has generality to human behavior.     

Effects of d-amphetamine, cocaine, and phencyclidine on the acquisition of response sequences with and without stimulus fading.

In each of three components of a multiple schedule, monkeys were required to emit a different sequence of four responses in a predetermined order on four levers. Sequence completions produced food on a fixed-ratio schedule. Errors produced a brief timeout. One component of the multiple schedule was a repeated-acquisition task where the four-response sequence changed each session (learning). The second component of the multiple schedule was also a repeated-acquisition task, but acquisition was supported through the use of a stimulus-fading procedure (faded learning). In a third component of the multiple schedule, the sequence of responses remained the same from session to session (performance). At higher doses, d-amphetamine, cocaine, and phencyclidine decreased the overall rate of responding and increased the percent errors in all three components. At lower doses, however, the three drugs produced selective effects on errors. Errors were increased in the learning component at lower doses than those required to disrupt the behavior in the faded-learning component. The performance component tended to be the least sensitive to disruptive drug effects. The data are consistent with the view that stimulus fading can modulate the effects of drugs on acquisition.     

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.     

Differential antagonism of cocaine self-administration and cocaine-induced disruptions of learning by haloperidol in rhesus monkeys

Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032-0.032 mg/kg/infusion of cocaine increased response rate and the number of infusions in the self-administration component when compared to saline administration, whereas 0.1-0.32 mg/kg/infusion decreased response rate and the number of infusions. When compared to saline administration, the two lowest infusion doses of cocaine had little or no effect on responding in the acquisition and performance components; however, higher infusion doses of cocaine dose-dependently decreased response rate in these components. In addition, the higher doses of cocaine also increased the percentage of errors in the acquisition and performance components. Pretreatment with haloperidol (0.0032 or 0.01 mg/kg, i.m.) antagonized the effects of low doses of cocaine on the number of infusions in the self-administration component, whereas only the 0.01-mg/kg dose antagonized the effects of high doses of cocaine on the number of infusions. Neither dose of haloperidol antagonized the rate-decreasing effects of cocaine on responding in the acquisition and performance components significantly; the highest dose of haloperidol alone decreased rates of responding in each component. Antagonism of cocaine's error-increasing effects by haloperidol was only evident at one dose of cocaine (0.032 mg/kg/infusion), and was more complete in the performance components than in the acquisition components. Together, these data show the limited suitability of haloperidol for selectively antagonizing cocaine self-administration in the context of a multiple schedule involving transition behavior, and show the lack of uniform antagonism across operant behaviors.     

Effects of cocaine and d-amphetamine on the repeated acquisition and performance of conditional discriminations.

The acute and chronic effects of cocaine and d-amphetamine on food-reinforced behavior were investigated in pigeons responding on a two-component multiple schedule. In one component, the behavioral task consisted of the same chain of conditional discriminations each session (performance). In the other component, the chain of conditional discriminations was changed from session to session (learning). In comparison to control sessions, both acute cocaine and d-amphetamine increased errors in each component of the multiple schedule. Responding in the learning component, however, was generally disrupted at lower doses than those that affected responding in the performance component. At high doses, both drugs produced pauses in responding in each component in three of the four subjects. Pausing engendered by d-amphetamine was approximately twice as long as that under cocaine. Upon chronic administration, both the pausing and error-increasing effects of each drug diminished. Drug-induced changes in timeout responding, however, did not decrease during chronic administration. Redeterminations of the d-amphetamine dose-effect curves following chronic cocaine administration suggested the existence of cross-tolerance between cocaine and d-amphetamine. Both the acute and chronic data are consistent with the view that conditions of stimulus control may modulate the behavioral effects of drugs.     

Interactions in multiple schedules: negative induction with squirrel monkeys

In Experiment I, lever pressing by squirrel monkeys was maintained under a sequence of variable-interval, multiple variable-interval variable-interval, and multiple variable-interval extinction schedules of food presentation. Negative induction (decreased responding in the unchanged component) occurred when one component of the multiple variable-interval variable-interval schedule was changed to extinction. Negative induction was transient over sessions; responding in the unchanged component usually recovered to a rate similar to that under the multiple variable-interval variable-interval schedule. Negative induction was not accompanied by consistent changes in the patterns of local responding within the unchanged component, and did not depend on whether component schedules were associated with localized (lever lights) or diffuse visual stimuli (houselights), or on whether the unchanged component was a 60- or 180-sec variable-interval schedule. In Experiment II, responding was maintained under a sequence of variable-interval and multiple variable-interval timeout schedules of food presentation. Negative induction occurred when responding declined gradually in the timeout component but not when responding declined abruptly. The nature of interactions in multiple schedules may depend on the species; negative induction was observed with squirrel monkeys under conditions similar to those that produce positive contrast with pigeons.     

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 ratio reinforcement schedules on discrimination performance by Japanese monkeys

In Experiment 1, Japanese monkeys were trained on three conditional position-discrimination problems with colors as the conditional cues. Within each session, each problem was presented for two blocks of ten reinforcements; correct responses were reinforced under continuous-reinforcement, fixed-ratio 5, and variable-ratio 5 schedules, each assigned to one of the three problems. The assignment of schedules to problems was rotated a total of three times (15 sessions per assignment) after 30 sessions of acquisition training. Accuracy of discrimination increased to a moderate level with fewer trials under CRF than under ratio schedules. In contrast, the two ratio schedules, fixed and variable, were more effective in maintaining accurate discrimination than was CRF. With further training, as asymptotes were reached, accuracy was less affected by the schedule differences. These results demonstrated an interaction between the effects of reinforcement schedules and the level of acquisition. In Experiment 2, ratio sizes were gradually increased to 30. Discrimination accuracy was maintained until the ratio reached 20; ratio 30 strained the performance. Under FR conditions, accuracy increased as correct choice responses cumulated after reinforcement.     

Alternative response training, differential reinforcement of other behavior, and extinction in squirrel monkeys (Saimiri sciureus)

In Experiment I, (a) extinction, (b) extinction plus reinforcement of a discrete alternative response, and (c) differential reinforcement of other behavior were each correlated with a different stimulus in a three-component multiple schedule. The alternative-response procedure more rapidly and completely suppressed behavior than did differential reinforcement of other behavior. Differential reinforcement of other behavior was slightly more effective than extinction alone. In Experiment II, reinforcement of specific alternative behavior during extinction and differential reinforcement of other behavior were used in two components, while one component continued to provide reinforcement for the original response. Once again, the alternative-response procedure was most effective in reducing responding as long as it remained in effect. However, the responding partially recovered when reinforcement for competing behavior was discontinued. In general, responding was less readily reduced by differential reinforcement of other behavior than by the specific alternative-response procedure.     

Drug effects on repeated acquisition: comparison of cumulative and non-cumulative dosing

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of a sequence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. Each day there were four 15-minute sessions, with a 10-minute inter-session interval. Cumulative dose-effect curves for phencyclidine, pentobarbital, and d-amphetamine were obtained by giving an injection before each of the four sessions; successive injections increased the cumulative dose in equally spaced logarithmic steps. For comparison, non-cumulative doses of each drug (i.e., doses not preceded by other doses on the same day) were also tested. As the cumulative dose of each drug increased, the overall response rate decreased, the percent errors increased, and there was less within-session error reduction (acquisition). With phencyclidine and pentobarbital, the rate-decreasing and error-increasing effects tended to be greater with a non-cumulative dose than with the corresponding cumulative dose. In contrast, with d-amphetamine, the effects were considerably greater with the cumulative doses. The results indicate that although the cumulative-dosing procedure saved a substantial amount of time in determining dose-effect curves, there were quantitative differences in effects between cumulative and non-cumulative doses.     

Effects of morphine, clonidine, and intensity change on electric-shock discrimination.

The effects of morphine, clonidine, and changes in stimulus intensity were examined in squirrel monkeys responding on one of two levers following brief presentations of one of two electric-shock intensities (0.1 and 0.5 mA). Responses were designated as correct or incorrect depending on which shock intensity had been presented and which lever was pressed. Morphine (0.42 to 1.80 mg/kg) and clonidine (0.075 to 0.18 mg/kg) decreased percentage correct responding. Morphine and clonidine also increased response latency and the number of shock presentations that were not followed by responses. Changes in shock intensity also decreased percentage correct responding but had no effect on response latency or on the number of shock presentations not followed by responses.     

Tolerance to and residual effects of cocaine in squirrel monkeys depend on reinforcement-schedule parameter.

Lever pressing by 4 squirrel monkeys was maintained under a three-component multiple fixed-ratio schedule of food presentation; components differed with respect to ratio size. For each monkey, acute administration of cocaine (0.03 to 1.3 mg/kg, i.m.) produced dose-dependent decreases in overall response rate in each component. During repeated daily administration of 1.0 mg/kg of cocaine, tolerance developed to the rate-decreasing effects under each of the ratio contingencies, but developed to a greater extent and was evident in earlier parts of sessions for performance under the smaller ratios. Response rates of 2 monkeys increased above nondrug control levels despite the putative reinforcer not being consumed during the session. When saline or a smaller dose of cocaine was substituted for 1.0 mg/kg, response rates often were suppressed below nondrug control-level responding. This suppressive effect was observed in each monkey and was more likely to be observed and/or to be of greater magnitude in large-ratio components for 3 of the 4 monkeys. When saline was administered chronically at the end of the chronic-drug phase, response rates remained suppressed in the large-ratio component for 2 of the monkeys. There was, therefore, a schedule-dependent dissociation between behavioral tolerance and the residual effects: Tolerance was greater when small ratios were arranged, whereas the residual effects were more pronounced when larger ratios were arranged.     

Effects of scopolamine on repeated acquisition of radial-arm maze performance by rats.

Rats repeatedly acquired the performance of selecting only the four baited arms in an automated eight-arm radial maze, with the arms containing food pellets randomly assigned prior to each session. During each 14-trial (trial: obtain all four pellets) daily session, the number of errors (selecting nonbaited arms or repeating arm selections) showed a within-session decline, and choice accuracy for the first four arm selections showed a positive acceleration across trials for all rats. An index-of-curvature statistic, calculated for total errors, was used to quantify both the within- and between-session improvement of performance. Scopolamine (0.03 to 0.3 mg/kg, ip), but not methylscopolamine (0.3 mg/kg), reduced the accuracy of the first four selections of each trial and increased total within-session errors for all rats. Session times also were increased by scopolamine. An examination of within-session accuracy showed only slight signs of improvement at the higher dosages of scopolamine. The results indicate that behavior in transition states maintained by reinforcement contingencies in the radial maze is similar to that maintained by extended chained schedules, despite the fact that some of the stimuli controlling behavior in the maze are absent at the moment behavior is emitted.     

A comparison of forward and backward procedures for the acquisition of response chains in humans

Ten university students each learned four separate six-link response chains, two forward and two backward. All 10 subjects made fewer errors in the forward procedure. It was concluded that the forward procedure is superior because each link of the response chain is acquired by direct reinforcement.     

Symmetry and transitivity of conditional relations in monkeys (Cebus apella) and pigeons (Columba livia)

In Experiment 1 six monkeys were tested with discriminative relations that were backward relative to their training in a 0-second conditional (“symbolic”) matching procedure. Although there was some indication of backward associations, the evidence was generally weak, and statistical evaluations did not reach conventional significance levels. Unlike children, who show backward associations to the point of symmetry, monkeys and pigeons display at best only weak and transient backward associations. In Experiment 2 associative transitivity was assessed across two sets of conditional matching tasks. All four monkeys tested demonstrated strong transitivity. In contrast, in Experiment 3 there was no evidence of transitivity in three pigeons tested under conditions closely comparable to those of Experiment 2. These results may identify some key features of interspecies differences and contribute to analyses of serial learning in animals.     

Effects of D-amphetamine on response acquisition with immediate and delayed reinforcement.

The present study examined in 8-hour sessions the effects of d-amphetamine (1.0, 5.6, and 10 mg/kg) on the acquisition of lever-press responding in rats that were exposed to procedures in which water delivery was delayed by 0, 8, or 16 seconds relative to the response that produced it. Both nonresetting- and resetting-delay conditions were studied. Although neither shaping nor autoshaping occurred, substantial levels of operative-lever responding developed under all conditions in which responses produced water. The lowest dose (1.0 mg/kg) of d-amphetamine either had no effect on or increased operative-lever pressing, whereas higher doses typically produced an initial reduction in lever pressing. Nonetheless, overall rates of operative-lever pressing at these doses were as high as, or higher than, those observed with vehicle. Thus, response acquisition was observed under all reinforcement procedures at all drug doses. In the absence of the drug, most responding occurred on the operative lever when reinforcement was immediate. Such differential responding also developed under both nonresetting- and resetting-delay procedures when the delay was 8 seconds, but not when it was 16 seconds. d-Amphetamine did not affect the development of differential responding under any procedure. Thus, consistent with d-amphetamine's effects under repeated acquisition procedures, the drug had no detrimental effect on learning until doses that produced general behavioral disruption were administered.     

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.