Oral self-administration of pentobarbital by rhesus monkeys: relative reinforcing effects under concurrent fixed-ratio schedules.

During daily 3-hr sessions, orally delivered pentobarbital solutions and water, or two separate pentobarbital solutions, were concurrently available to rhesus monkeys according to fixed-ratio schedules of mouth contacts with a spout. First water, and then each of four "comparison-concentration" pentobarbital solutions (0.0625, 0.25, 1, and 4 mg/mL), was successively available from one spout for a block of sessions under a fixed-ratio-64 (three monkeys) or fixed-ratio-16 (one monkey) schedule. Under an identically sized fixed-ratio schedule, deliveries of a "standard-concentration" pentobarbital solution were concurrently available from a second spout. The concentration of the standard solution remained unchanged throughout testing of the series of comparison solutions. Each of three pentobarbital concentrations (4, 1, and 0.25 mg/mL) in turn served as the standard concentration. Within each pair of concurrently available solutions, the higher drug concentration maintained more behavior than the lower concentration. Thus when monkeys were provided with concurrent access to different pentobarbital concentrations, relative reinforcing effects were directly related to drug concentration. Further, the amount of behavior maintained by a particular drug concentration was dependent on the concentration of the concurrently available drug solution. Thus, the relative effectiveness of a reinforcer in maintaining behavior is a function of both the reinforcer's magnitude and the availability of alternative reinforcers in the environment.     

Oral drug self-administration in rhesus monkeys: interactions between drug amount and fixed-ratio size.

During daily 3-hr sessions, 5 rhesus monkeys drank drug solutions and water that were concurrently available. The drug solutions were: 1 milligram per milliliter (mg/mL) pentobarbital (2 monkeys), 1 mg/mL pentobarbital plus 0.5% ethanol (1 monkey), 1 mg/mL pentobarbital plus 1% ethanol (1 monkey), and 8% ethanol (1 monkey). The drug solution and water were available under identical two-component tandem fixed-ratio continuous-reinforcement N schedules. Two variables were manipulated: the size of the fixed-ratio component and the number of liquid deliveries (N) in the second component. Deliveries of the drug solution maintained higher rates of responding than did deliveries of the drug vehicle, water. The number of drug deliveries per session increased with increases in the number of deliveries per fixed ratio and decreased with increases in fixed-ratio size. Analysis of the results in terms of the proportion of deliveries to responses showed that the number of drug deliveries per session was directly related to the size of this quotient. Finally, when fixed-ratio size was repeatedly doubled, the following orderly relationship emerged: The greater the number of available drug deliveries per fixed ratio, the less was the percent decrease in the number of fixed ratios completed per session. It was concluded that increases in the number of liquid deliveries per fixed ratio resulted in increases in reinforcing efficacy.     

Oral self-administration of pentobarbital by rhesus monkeys: maintenance of behavior by different concurrently available volumes of drug solution.

For 4 rhesus monkeys, mouth-contact responses with either of two brass spouts were reinforced according to fixed-ratio schedules by 0.65-mL liquid deliveries during daily 3-hr sessions. Three experiments were conducted. In each experiment, independent fixed-ratio schedules were concurrently in effect at the two spouts. Following completion of each fixed ratio on a spout, a specified number of liquid deliveries were available from that spout under a continuous-reinforcement schedule. The number of such deliveries available at each spout was manipulated independently. In Experiment 1, a 1-mg/mL pentobarbital solution was simultaneously available with water (the drug vehicle) under concurrent fixed-ratio schedules of 32 responses for 3 subjects and 64 responses for the remaining subject. The number (N) of liquid deliveries that were available after completion of each fixed ratio was varied in the following order: 8, 4, 2, 1, and 8 (retest). For each subject at each condition, drug maintained more responding than water. The number of drug deliveries obtained per session was directly related to the amount of drug available per fixed ratio (i.e., to N), whereas the number of fixed ratios completed per session generally was inversely related to the value of N. In Experiment 2, fixed-ratio size was the same for each subject as in Experiment 1, but deliveries of a 1-mg/mL pentobarbital solution were available at both spouts. The number of drug deliveries available under one fixed-ratio schedule (Ns, the "standard" reinforcer amount) was held at eight, and the number of drug deliveries available under the second schedule (Nc, the "comparison" reinforcer amount) was changed across blocks of six sessions of stable responding in the following order: 1, 2, 4, 8, 4, 2, and 1. The identical series of comparison reinforcer amounts (Nc) was then tested twice more, but with the standard reinforcer (Ns) held first at four and then at two deliveries. Across the three choice series, reinforcing effects were directly related to reinforcer magnitude. In Experiment 3, deliveries of a 1-mg/mL pentobarbital solution again were available at both spouts. However, the two reinforcer amounts were held constant at N = 8 deliveries under one schedule and N = 4 deliveries under the second schedule, and fixed-ratio size was systematically varied. Across the range of fixed-ratio sizes from low to high, the degree to which behavior was better maintained by the larger of the two drug quantities was an inverted U-shaped function of fixed-ratio size.(ABSTRACT TRUNCATED AT 400 WORDS)     

Modifying drug-reinforced behavior by altering the economic conditions of the drug and a nondrug reinforcer.

Six rhesus monkeys were trained to self-administer orally delivered phencyclidine (0.25 mg/mL) and saccharin (0.03% wt/vol) under concurrent fixed-ratio 16 schedules. In Condition 1 the fixed-ratio requirement for phencyclidine was changed from 16 to 4, 8, 16, 32, 64, 128 and 16 while the fixed-ratio requirement for saccharin deliveries remained constant at 16. In Condition 2 the fixed-ratio value for saccharin was systematically altered while the fixed-ratio requirement for phencyclidine remained at 16, and in Condition 3 the fixed-ratio requirements for both phencyclidine and saccharin were altered simultaneously. Water was then substituted for saccharin, and the series of fixed-ratio manipulations was replicated. The phencyclidine concentration was reduced to 0.125 mg/mL and Conditions 1 and 3 were repeated. When the fixed-ratio requirement for phencyclidine was increased and the fixed-ratio requirement for saccharin or water remained fixed at 16, phencyclidine deliveries decreased when saccharin (vs. water) was concurrently available. The magnitude of the decrease ranged from 20% to 90% (of the concurrent water condition) as the fixed-ratio requirement for phencyclidine increased from 4 to 128. When the fixed-ratio requirement for phencyclidine remained at 16 and the fixed-ratio requirements for concurrent saccharin or water varied between 4 and 128, phencyclidine deliveries decreased by 30% to 40% due to the concurrent availability of saccharin (vs. water). This decrease occurred only at the three lowest fixed-ratio values when saccharin intake was relatively high. When the fixed-ratio requirements for both phencyclidine and concurrent saccharin or water were varied simultaneously, phencyclidine deliveries were reduced from 20% to 45% when saccharin (vs. water) was concurrently present. There was little effect of reducing the phencyclidine concentration when the data were analyzed in terms of unit price (responses per milligram). Thus, changes in the fixed-ratio requirement or drug concentration were functionally similar, and unit price of phencyclidine was the variable that was influenced by the presence of concurrent saccharin. These data indicate that drug-reinforced behavior is substantially reduced when the environment is enriched with an alternative nondrug reinforcer. The economic context in which these substances are presented is an important determinant of drug-reinforced behavior.     

Ratio size and cocaine concentration effects on oral cocaine-reinforced behavior.

Monkeys were given a choice between cocaine solutions and water under concurrent fixed-ratio reinforcement schedules. The operant response was spout contact. Six rhesus monkeys served as subjects. The cocaine concentration was varied from 0.0125 to 0.8 mg/ml, and the fixed-ratio value was varied from 8 to 128. Cocaine maintained higher response rates than did water over a wide range of conditions. Response rate and number of cocaine deliveries per session were inverted U-shaped functions of concentration. These functions were shifted to the right as the fixed ratio was increased. The number of cocaine deliveries was more persistent as fixed-ratio value was increased when the unit dose was larger rather than smaller. Cocaine consumption was analyzed as a function of unit price (fixed-ratio value divided by cocaine concentration), and unit price accounted for between 77% and 92% of the variance in cocaine consumption for individual monkeys. The current data support the claim that a drug's reinforcing effects increase directly with dose and underscore the need to gather parametric data when examining the effects of experimental manipulations on a drug-reinforced baseline.     

Relative reinforcing effects of different oral ethanol doses in rhesus monkeys

The relative reinforcing effects of different doses of orally delivered ethanol were evaluated. Mouth-contact responding by rhesus monkeys was measured under concurrent fixed-ratio fixed-ratio schedules of liquid delivery (0.67 ml/delivery) from each of two spouts during daily 3-hr sessions. Experiment 1 examined persistence of responding with ethanol (2%, 8%, and 32% wt/vol) and water available. When fixed-ratio values from 8 to 128 were tested, the number of ethanol deliveries obtained per session decreased as the response requirement increased. The decrease in deliveries was less at higher than at lower ethanol concentrations, however. Experiment 2 examined choice between two ethanol concentrations under concurrent fixed-ratio 16 schedules (4% vs. 8%, 4% vs. 16%, 8% vs. 16%, 2% vs. 8%, 2% vs. 32%, 8% vs. 32%). Higher concentrations (16%, 32%) generally maintained more responding than concurrently available concentrations of 8% or less. An exception was the observation of a preference for 8% over 32% ethanol. When the fixed-ratio value was increased, however, the relative preference for these two doses was reversed so that 32% ethanol maintained more responding than 8% ethanol. Thus, the direction of the preference depended on the size of the response requirement. These results indicate that the reinforcing effects of ethanol increase with dose.     

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

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

Matching under nonindependent variable-ratio schedules of drug reinforcement.

Response-contingent deliveries of oral pentobarbital maintained responding of 3 rhesus monkeys during daily 3-hr sessions. Deliveries of pentobarbital were arranged under nonindependent concurrent variable-ratio variable-ratio schedules. Responses to either schedule counted toward completion of both variable-ratio schedule requirements. This schedule is similar in some respects to conventional concurrent variable-interval variable-interval schedules, in which passage of time counts toward completion of the interval value on both schedules. Restricted nonindependent concurrent variable-ratio variable-ratio schedules were also studied. On that schedule, when a drug delivery was assigned to one spout, it had to be collected before responses on the opposite spout again counted toward completion of the schedule requirements. Relative reinforcer magnitude was varied by changing the drug concentration on one schedule while keeping the drug concentration constant on the other variable-ratio schedule. Under both types of concurrent variable-ratio schedules, the relative rate of responding corresponded to the relative drug intake. Unlike earlier studies of concurrent variable-interval variable-interval intravenous cocaine reinforcement, preference was proportionate to concentration, and exclusive preferences did not develop. The relationship between relative rate of responding and relative drug intake was well described by the generalized matching law.     

Concurrent access to two concentrations of orally delivered phencyclidine: effects of feeding conditions.

Two experiments addressed the effects of food satiation and deprivation on oral self-administration of two concurrently available phencyclidine concentrations. In the first experiment, 8 rhesus monkeys self-administered either of two concentrations of phencyclidine ("PCP, angel dust") and water under concurrent fixed-ratio 16 schedules. One concentration was always held constant (0.25 mg/mL) while a series of other phencyclidine concentrations, ranging from 0 (water) to 1.0 mg/mL, was presented in a nonsystematic order. Initially the monkeys were tested while food satiated, and the procedure was then repeated during food deprivation. The monkeys usually selected the higher concentration within the first few minutes of the session, indicating that taste and/or other immediate postingestional effects were important factors. Contrary to a number of previous reports, there were no consistent differences across subjects in the mean number of liquid deliveries or mean drug intake (mg/kg) during food satiation and deprivation. However, for all monkeys the within-session time course of responding during food satiation consistently differed from that during deprivation. A second experiment assessed whether the failure to find consistent differences in drug intake during food satiation and deprivation had been due to the history of concurrent access to different phencyclidine concentrations or to the extended experience with phencyclidine under food-satiation conditions. Six additional monkeys (Group 2) were exposed to the phencyclidine self-administration procedure (during food satiation and deprivation) for the same length of time as the monkeys in Experiment 1 (Group 1), except they received only concurrent access to phencyclidine (0.25 mg/mL) and water. Both groups then received concurrent access to phencyclidine and water during five repeated cycles of food deprivation and satiation. There were also marked individual differences in Group 2: During food satiation, 2 of the monkeys' responding increased, 1 showed no change, and 3 decreased. Examination of a number of historical variables indicated that the greater the percentage of total sessions spent during food satiation with phencyclidine available (before these experiments began), the greater the amounts of phencyclidine consumed during food satiation and the smaller the differences in phencyclidine intake when the two feeding conditions were compared.     

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.     

Drug discrimination under concurrent variable-ratio variable-ratio schedules

Pigeons were trained to discriminate 5 mg/kg pentobarbital from saline under concurrent variable-ratio (VR) VR schedules, in which responses on the pentobarbital-biased lever were reinforced under the VR schedule with the smaller response requirements when pentobarbital was given before the session, and responses on the saline-biased key were reinforced under the VR schedule with the larger response requirements. When saline was administered before the session, the reinforcement contingencies associated with the two response keys were reversed. When responding stabilized under concurrent VR 20 VR 30, concurrent VR 10 VR 40, or concurrent VR 5 VR 50 schedules, pigeons responded almost exclusively on the key on which fewer responses were required to produce the reinforcer. When other doses of pentobarbital and other drugs were substituted for the training dose, low doses of all drugs produced responding on the saline-biased key. Higher doses of pentobarbital and chlordiazepoxide produced responding only on the pentobarbital-biased key, whereas higher doses of ethanol and phencyclidine produced responding only on this key less often. d-Amphetamine produced responding primarily on the saline-biased key. When drugs generalized to pentobarbital, the shape of the generalization curve under concurrent VR VR schedules was more often graded than quantal in shape. Thus, drug discrimination can be established under concurrent VR VR schedules, but the shapes of drug-discrimination dose-response curves under concurrent VR VR schedules more closely resemble those seen under interval schedules than those seen under fixed-ratio schedules. Graded dose-response curves under concurrent VR VR schedules may relate to probability matching and difficulty in discriminating differences in reinforcement frequency.     

Pentobarbital and d-amphetamine effects on concurrent performances.

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

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.     

Second-order schedules with fixed-ratio components: variation of component size

Key pecking by pigeons was reinforced with food under second-order schedules with fixed-ratio units. A constant total number of key pecks was required for reinforcement under each condition, but the size and, inversely, number of fixed-ratio components were varied. The total response requirement of 256 pecks was divided into fixed-ratio units of 128, 64, 32, 8, and 2 responses. A brief stimulus, which always preceded food reinforcement, was presented upon completion of each fixed-ratio unit. Under most conditions, the pattern of within-unit responding was typical of that under simple fixed-ratio schedules. Overall response rate was an inverted U-shaped function of component size. That is, response rates were highest under moderate sized units (fixed ratio 128 and 64). This relationship is consistent with previous determinations of rate as a function of fixed-ratio value for simple fixed-ratio schedules.     

Effects of d-amphetamine and pentobarbital under concurrent fixed-ratio schedules.

Pigeons were studied under a two-key concurrent fixed-ratio schedule of food presentation. During the first five sessions, the fixed-ratio requirements were 30 responses on one key (major key) and 120 responses on the other key (minor key): responding occurred almost exclusively on the major key. When the fixed-ratio requirements were then made equal at 30 responses on both keys, responding continued to predominate on the major key. The asymmetric distribution of responses persisted when the concurrent fixed-ratio fixed-ratio schedule was interrupted with periods during which the major key was associated with extinction while the other key remained associated with a fixed-ratio schedule. Additionally, in some subjects the fixed-ratio requirements were increased. These schedule modifications decreased the asymmetry in responding but did not eliminate it. d-Amphetamine decreased rates on both keys and slightly increased the asymmetric distribution of responses, while pentobarbital reversed the distribution of responses by increasing low rates and decreasing high rates. The pigeons maintained their original asymmetric distribution of responses during the 1 1/2-year-long study, despite schedule alterations and drug administrations.     

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.     

Concept learning set‐size functions for Clark's nutcrackers

Same/Different abstract‐concept learning by Clark's nutcrackers (Nucifraga columbiana) was tested with novel stimuli following learning of training set expansion (8, 16, 32, 64, 128, 256, 512, and 1024 picture items). The resulting set‐size function was compared to those from rhesus monkeys (Macaca mulatta), capuchin monkeys (Cebus apella), and pigeons (Columba livia). Nutcrackers showed partial concept learning following initial eight‐item set learning, unlike the other species (Magnotti, Katz, Wright, & Kelly, 2015). The mean function for the nutcrackers' novel‐stimulus transfer increased linearly as a function of the logarithm of training set size, which intersected its baseline function at the 128‐item set size. Thus, nutcrackers on average achieved full concept learning (i.e., transfer statistically equivalent to baseline performance) somewhere between set sizes of 64 to 128 items, similar to full concept learning by monkeys. Pigeons required a somewhat larger training set (256 items) for full concept learning, but results from other experiments (initial training and transfer with 32‐ and 64‐item set sizes) suggested carryover effects with smaller set sizes may have artificially prolonged the pigeon's full concept learning. We find it remarkable that these diverse species with very different neural architectures can fully learn this same/different abstract concept, and (at least under some conditions) do so with roughly similar sets sizes (64‐128 items) and numbers of training exemplars, despite initial concept learning advantages (nutcrackers), learning disadvantages (pigeons), or increasing baselines (monkeys).     

Drug discrimination under two concurrent fixed-interval fixed-interval schedules

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.     

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.     

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.