Effects of schedule of reinforcement on a pentobarbital discrimination in rats.

The purpose of this study was to determine the effects of the schedule of reinforcement on a pentobarbital discrimination in rats. Five rats were trained to discriminate 10 mg/kg pentobarbital from saline under a multiple fixed-interval 180-s fixed-ratio 20 schedule of reinforcement. During both saline and pentobarbital training sessions, subjects emitted a higher percentage of correct responses under the fixed-ratio component as compared to the fixed-interval component of the multiple schedule. Determination of the pentobarbital dose-response curve under the fixed-ratio component resulted in a steep curve characterized by responding on the saline lever at low doses and on the drug lever at higher doses. Under the fixed-interval component, a graded dose-effect curve was produced, with considerable responding on both levers after intermediate doses of pentobarbital. The administration of phencyclidine and MK-801 resulted in an intermediate level of drug-lever responding for some subjects. Administration of d-amphetamine resulted in saline (nondrug) appropriate responding. The results of this study demonstrate that the schedule of reinforcement is a determinant of drug stimulus control, just as it is a determinant of other drug effects.     

Effects of ethanol on multiple fixed-interval fixed-ratio schedule performances: dynamic interactions at different fixed-ratio values.

Key pecking by three pigeons was maintained under a multiple fixed-interval fixed-ratio schedule of food presentation. The fixed-interval value remained at 3 minutes, while the fixed-ratio size was increased systematically in 30-response increments from 30 to either 120 (two pigeons) or 150 (one pigeon). At least two lower fixed-ratio values were also redetermined. The effects of ethanol (5 to 2.5 g/kg) were assessed at each of the different schedule parameters. Both overall and running response rates under the fixed-ratio schedule decreased with increases in the size of the fixed-ratio schedule; pause duration under the fixed-ratio schedule was directly related to increases in fixed-ratio size. Overall and running rates of responding under the fixed-interval schedule changed little with increases in the size of the fixed-ratio schedule. Despite the relative invariance of fixed-interval responding across the different fixed-ratio values, the effects of ethanol on responding under the fixed-interval schedule differed depending on the size of the fixed-ratio schedule. Greater increases occurred in both overall and in lower local rates of responding under the fixed-interval schedule when the fixed-ratio value was 120 or 150. The effects of ethanol on responding under the fixed-ratio schedule also depended on the size of the fixed ratio. Increases in responding under the fixed-ratio schedule were typically greater at the higher fixed-ratio values where response rates were lower. When the effects of ethanol were redetermined at the lower fixed-ratio parameter values, rates and patterns of responding were comparable to those obtained initially. However, the dose-effect curves for responding under both fixed-ratio and fixed-interval schedules were shifted up and to the right of those determined during the ascending series. The effects of ethanol can depend on rate or responding, behavioral history, and the context in which behavior occurs.     

The effects of schedule history and the opportunity for adjunctive responding on behavior during a fixed-interval schedule of reinforcement.

The effects of schedule history and the availability of an adjunctive response (polydipsia) on fixed-interval schedule performance were investigated. Two rats first pressed levers under a schedule of food reinforcement with an interresponse time greater than 11 s, and 2 others responded under a fixed-ratio 40 schedule. All 4 were then exposed to a fixed-interval 15-s schedule. Water was continuously available under these conditions, but after responding became stable on the fixed-interval schedule, access was experimentally manipulated. With water freely available, subjects did not display characteristic fixed-interval response rates and patterns (i.e., scalloping or break-and-run). Instead, they exhibited predictable, stable patterns of behavior as a function of their schedule histories: Subjects with the interresponse-time history exhibited low response rates, and those with the fixed-ratio history exhibited high rates. Manipulating the amount of water available resulted in marked changes in response rates for rats with the interresponse-time history but not for those with the fixed-ratio history. The results illustrate the multiple causation of behavior by its previous and current schedules of reinforcement and other concurrent factors.     

Interaction of methadone, reinforcement history, and variable-interval performance.

In the present study, we examined how a reinforcement schedule history that generated high or low rates of responding influenced the effects of acute (Experiment 1) and chronic (Experiment 2) methadone administration. Initially, key-peck responses of pigeons were maintained under a variable-interval 90-s schedule of food presentation, and a methadone dose-response curve was determined with doses of 0.6, 1.2, and 2.4 mg/kg. The pigeons were then exposed, for at least 40 sessions, to either a fixed-ratio 50 schedule or a differential-reinforcement-of-low-rate 10-s schedule, or were given continued exposure to the variable-interval schedule. The methadone dose-response curve was redetermined after all pigeons again were responding under the variable-interval schedule. The effects of two different daily methadone doses (9.0 and 12.0 mg/kg/day) and withdrawal precipitated by naloxone also were assessed. Experience with a fixed-ratio or differential reinforcement of low rate schedule did not result in significantly different response rates under the variable-interval schedule and, in general, the acute effects of methadone did not have differential effects correlated with schedule history. However, for 2 of 4 subjects the rate-decreasing effects of methadone on rates of key pecking were greater following a history of low-rate responding, suggesting a possible interaction between schedule history and effects of methadone. Daily methadone administration under the variable-interval schedule revealed that pigeons with experience under the differential reinforcement of low rate schedule developed more rapid and complete tolerance to the rate-decreasing effects of methadone. Three of the 4 subjects in this group showed rate increases above drug-free baselines during chronic methadone dosing. Pigeons with a history of fixed-ratio responding also developed tolerance to the rate-decreasing effects of methadone but without the subsequent rate increases seen by subjects with low-rate histories. No subjects with variable-interval histories showed complete recovery of drug-free baselines, suggesting that interpolated training under other schedules may attenuate the rate-altering effects of chronically administered drugs. Naloxone (1.0 mg/kg), administered during the chronic methadone phase, resulted in greater disruption of responding by pigeons with a history of low-rate responding, as compared to subjects in the other two groups.(ABSTRACT TRUNCATED AT 400 WORDS)     

Low-response-rate conditioning history and fixed-interval responding in rats.

Bar presses by one group of rats were conditioned under a differential-reinforcement-of-low-rate reinforcement schedule immediately prior to conditioning under a fixed-interval schedule. In a second group of rats, bar presses were conditioned first under a differential-reinforcement-of-low-rate schedule and then under a fixed-ratio schedule prior to conditioning under a fixed-interval schedule. Low response rates occurred under the fixed-interval schedule only when it was immediately preceded by low-rate conditioning. Otherwise, fixed-interval responding was similar to responding under the fixed-ratio schedule. This finding suggests that responses of laboratory animals are sensitive to immediate history, and, unlike human responses, are relatively insensitive to a history of low-rate conditioning when it is followed by high-rate conditioning.     

An inverse relationship between baseline fixed-interval response rate and the effects of a tandem response requirement.

Previous experiments examining the effects of adding a tandem fixed-ratio response requirement on fixed-interval schedule performance have reported inconsistent results. One variable that may account for such inconsistencies is the baseline response rate in the fixed-interval condition. This possibility was investigated in the present study. Rats were given histories with either interresponse times greater than 11 s or fixed-ratio 40 schedules of reinforcement, which engendered either relatively low or high rates of responding, respectively, in the subsequent fixed-interval condition. A tandem ratio response requirement (fixed-ratio 9) was then introduced. The effects of adding this tandem response requirement were inversely related to the baseline fixed-interval response rates; low rates of responding in the fixed-interval condition were markedly increased, whereas high rates of responding were relatively unaffected. This inverse relationship appears to be similar to the rate-dependent relations observed in behavioral pharmacology. These results may provide an explanation for the inconsistent findings reported in previous studies on tandem fixed-interval fixed-ratio schedules and suggest that principles of behavioral pharmacology research may be applicable to the study of the effects of nonpharmacological variables on schedule-controlled behavior.     

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.     

Effects of methadone on alternative fixed-ratio fixed-interval performance: latent influences on schedule-controlled responding.

Effects of methadone on pigeons' key pecking were examined under four conditions selected to analyze the control of behavior under alternative fixed-ratio fixed-interval schedules. In Condition 1, pigeons pecked under one of three different alternative schedules (alternative fixed-ratio 50 fixed-interval 90 s, alternative fixed-ratio 75 fixed-interval 90 s and alternative fixed-ratio 200 fixed-interval 90 s) each week. In Condition 2, fixed-ratio 50 or fixed-ratio 75 schedules were in effect during baseline sessions, and alternative fixed-ratio 50 fixed-interval 90-s or alternative fixed-ratio 75 fixed-interval 90-s schedules were in effect during sessions in which methadone was administered. In Condition 3, effects of methadone on key pecking maintained under fixed-ratio 50 and fixed-ratio 75 schedules were examined, whereas in Condition 4 the effects of methadone on key pecking under a fixed-interval 90-s schedule as well as fixed-ratio 50 and fixed-ratio 75 schedules were investigated. Control by the fixed-interval contingency was assessed by computing the proportion of total session reinforcers delivered under the fixed-interval schedule. Methadone administration (0.5-4.0 mg/kg) shifted the predominant source of schedule control under the alternative schedule from the fixed-ratio schedule to the fixed-interval contingency. This shift was dependent on methadone dose and fixed-ratio size. Control by the fixed-interval contingency was greatest following extensive exposure to the interval component embedded within the alternative schedule (Condition 1), but was apparent to a lesser degree with even very limited exposure to the alternative fixed-ratio fixed-interval schedule (Condition 2). Interreinforcement intervals comparable to those under fixed-interval schedule were not observed under the fixed-ratio schedules presented alone (Condition 3). Repeated exposure to the fixed-interval contingency outside the context of the alternative fixed-ratio fixed-interval schedule did not engender performance changes under a fixed-ratio schedule which would mimic those of increased fixed-interval contingency control (Condition 4). These data suggest that drug administration can be used to unmask the influence of contingencies that are latent under baseline conditions and reveal influences of both past and present environmental variables.     

Remote effects of aversive contingencies: Disruption of appetitive behavior by adjacent avoidance sessions

Disruption of ongoing appetitive behavior before and after daily avoidance sessions was examined. After baselines of appetitive responding were established under a fixed-interval 180-s schedule of food presentation, 4 rats were exposed to 40-min sessions of the appetitive schedule just prior to 100-min sessions of electric shock postponement, while another 4 rats received the 40-min appetitive sessions just following daily sessions of shock postponement. In all 8 subjects, fixed-interval response rates decreased relative to baseline levels, the effect being somewhat more pronounced when the avoidance sessions immediately followed. The disruption of fixed-interval responding was only partially reversed when avoidance sessions were discontinued. During the initial exposure to the avoidance sessions, patterns of responding under the fixed-interval schedule were differentially sensitive to disruption, with high baseline response rates generally more disturbed than low rates. These disruptions were not systematically related to changes in reinforcement frequency, which remained fairly high and invariant across all conditions of the experiment; they were also not systematically related to the response rates or to the shock rates of the adjacent avoidance sessions. The results, while qualitatively resembling patterns of conditioned suppression as typically studied, occurred on a greatly expanded time scale. As disruption of behavior extending over time, the present data suggest that some forms of conditioned suppression are perhaps best viewed within a larger temporal context.     

Operant and nonoperant vocal responding in the mynah: Complex schedule control and deprivation-induced responding

Several recent studies have been concerned with operant responses that are also affected by nonoperant factors, (e.g., biological constraints, innate behavior patterns, respondent processes). The major reason for studying mynah vocal responding concerned the special relation of avian vocalizations to nonoperant emotional and reflexive systems. The research strategy was to evaluate operant and nonoperant control by comparing the schedule control obtained with the vocal response to that characteristic of the motor responses of other animals. We selected single, multiple, and chain schedules that ordinarily produce disparate response rates at predictable times. In multiple schedules with one component where vocal responding (“Awk”) was reinforced with food (fixed-ratio or fixed-interval schedule) and one where the absence of vocal responding was reinforced (differential reinforcement of other behavior), response rates never exceeded 15 responses per minute, but clear schedule differences developed in response rate and pause time. Nonoperant vocal responding was evident when responding endured across 50 extinction sessions at 25% to 40% of the rate during reinforcement. The “enduring extinction responding” was largely deprivation induced, because the operant-level of naive mynahs under food deprivation was comparable in magnitude, but without deprivation the operant level was much lower. Food deprivation can induce vocal responding, but the relatively precise schedule control indicated that operant contingencies predominate when they are introduced.     

Effects of methamphetamine and scopolamine on variability of response location.

Methamphetamine and scopolamine were studied in monkeys responding under a multiple fixed-ratio fixed-interval schedule of reinforcement. A response on any one of six levers could satisfy the schedule requirements. Variability of response location was evaluated in terms of switches, where a switch was defined as a response on one lever followed by a response on a different lever. Under baseline conditions the fixed-ratio schedule generated a high rate of responding and a low level of variability, while the fixed-interval schedule generated a low rate of responding and a high level of variability. Both methamphetamine (0.1 to 0.5 mg/kg) and scopolamine (2.4 to 240 microgram/kg) decreased overall response rate and increased variability of response location in each component of the multiple schedule with increasing doses of drug. At lower doses both drugs were found to decrease rate without affecting response variability.     

Effects of reinforcement history on responding under progressive-ratio schedules of reinforcement.

The effects of experimental history on responding under a progressive-ratio schedule of reinforcement were examined. Sixteen pigeons were divided into four equal groups. Groups 1 to 3 were trained to peck a key for food under a fixed-ratio, variable-ratio, or differential-reinforcement-of-low-rate schedule of reinforcement. After training, these pigeons were shifted to a progressive-ratio schedule, later were shifted back to their original schedule (with decreased rates of reinforcement), and finally were returned to the progressive-ratio schedule. Pigeons in Group 4 (control) were maintained on the progressive-ratio schedule for the entire experiment. To test for potential "latent history" effects, pigeons responding under the progressive-ratio schedule were injected with d-amphetamine and given behavioral-momentum tests of prefeeding and extinction. Experimental histories affected responding in the immediate transition to the progressive-ratio schedule; response rates of pigeons with variable-ratio and fixed-ratio histories were higher than rates of pigeons with differential-reinforcement-of-low-rate and progressive-ratio-only histories. Pigeons with differential-reinforcement-of-low-rate histories, and to a lesser degree pigeons with variable-ratio and fixed-ratio histories, also had shorter postreinforcement pauses than pigeons with only a progressive-ratio history. No consistent long-term effects of prior contingencies on responding under the progressive-ratio schedule were evident. d-Amphetamine and resistance-to-change tests failed to reveal consistent latent history effects. The data suggest that history effects are sometimes transitory and not susceptible to latent influences.     

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.     

Conjunctive schedules of reinforcement: I. Rate-dependent effects of pentobarbital and d-amphetamine

Key pecking of pigeons was maintained under conjunctive schedules of food presentation in which both a fixed-interval and a fixed-ratio schedule had to be completed before a peck produced food. For two pigeons, pecks on a single key completed both schedule requirements (fixed-interval 3-min, fixed-ratio 50 for one bird, fixed-interval 5-min, fixed-ratio 50 for the second). For two other pigeons, each requirement was scheduled on a separate key. On the two-key schedule, a peck after 5 min on the key scheduling the fixed-interval requirement produced food if at least 10 pecks had occurred on the ratio key (conjunctive fixed-interval 5-min, fixed-ratio 10). When each requirement was scheduled on a separate key, response rates on the fixed-ratio key were generally higher in the early portion of the interval and declined as the interval progressed; responding on the fixed-interval key, once initiated, typically remained at a constant rate throughout the interval. Responding under the single-key schedule was characterized by a high rate early in the interval; this then changed to a lower rate that continued until a peck produced food. For all pigeons, increases in response rates with pentobarbital and d-amphetamine were inversely related to the control rate of responding. When equivalent rates on each key of the two-key schedule were compared, both drugs increased rates on the fixed-ratio key less. Although the effects of both drugs were rate dependent, each drug differentially modified the pattern of responding under the single-key schedule.     

Schedule-induced defecation.

Excessive defecation, typically considered to be a concomitant of stress, was experimentally induced or eliminated under specific schedules of positive reinforcement of lever pressing by rats. The schedules were, by and large, those under which polydipsia is typically induced. In the first of three experiments, rats under fixed-interval 32-second schedules and variable interval 32-second schedules for food and water reinforcers defecated profusely, but not under fixed-interval one-second schedules or other small interval schedules. Somewhat higher rates of defecation were observed on variable interval 32-second schedules than on fixed-interval 32-second schedules. In a second experiment, fixed-ratio schedules were used, some of which resulted in responding such that reinforcement densities were similar to those on the interval schedules that induced defecation. Defecation was not systematically induced by these ratio schedules. In a third experiment, fixed-time schedules of food presentations were utilized. High rates of defecation were induced comparable to those induced by interval schedules of the same time parameter. No other behavior commonly termed "emotional" was observed in any of these experiments.     

The long-term effect of high- and low-rate responding histories on fixed-interval responding in rats

Tell rats were given extended lever-press training on a fixed-interval (FI) 30-s food reinforcement schedule from the outset or following exposure to one or two previous reinforcement schedules. For 4 rats the previots schedule was either fixed-ratio 20, which generated high response rates, or differential-reinforcement-of-low-rate 20 s, which produced low response rates. For 4 additional rats the extended training on FI 30 s was preceded by experience with two schedules: fixed-ratio 20 followed by differential-reinforcement-of-low-rate 20 s; or the same two schedules in the reverse order. Fixed-interval response rates were initially affected by the immediately preceding schedule, but after 80 to 100 sessions, all traces of prior schedule history had disappeared. The results also showed no long-term effect of schedule history on the interfood-interval patterns of responding on the FI 30-s schedule. These results support one of the most central tenets of the experimental analysis of behavior: control by the immediate consequences of behavior.     

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 d-amphetamine and caffeine on schedule-controlled and schedule-induced responding.

The effects of d-amphetamine and caffeine were studied on rates and patterns of lever pressing and schedule-induced licking under fixed-interval schedules of food pellet presentation. In addition, the effects of caffeine were studied on lever pressing and licking under a multiple fixed-ratio fixed-interval schedule. Caffeine reduced mean overall rates of licking at lower doses than it reduced mean overall rates of pressing under the fixed-interval schedules, but the effects of caffeine on both licking and lever pressing depended largely on the control rate of responding. d-Amphetamine reduced mean overall rates of lever pressing and licking at about the same dose, but the effects of d-amphetamine also were a function of the control rate of responding.     

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.