d-Amphetamine-chlorpromazine antagonism in a food reinforced operant

Dose effect curves for d-amphetamine and chlorpromazine were obtained with rats on a milk reinforced FR 10 schedule. A dose of d-amphetamine (2.5 mg/kg, i.p.) which completely suppressed all responding for 60 min was administered simultaneously (concomitant with the pretreatment times) with various doses of chlorpromazine. The d-amphetamine-induced cessation of responding was removed by several of the doses of chlorpromazine with maximal antagonism occurring at a dose of 1.5 mg/kg i.p. This dose of chlorpromazine, when administered independently, produced no observable side effects and showed no effect on the FR 10 schedule. One animal appeared to develop tolerance to the repeated dosages of d-amphetamine.     

Effects of chlordiazepoxide and d-amphetamine on responding suppressed by conditioned punishment

Key pecking by two pigeons, maintained under a variable-interval two-minute schedule of food presentation, was suppressed when each response produced a five-second visual stimulus that was occasionally paired with shock. Stimulus-shock pairings occurred independently of responding according to a variable-time six-minute schedule for one bird or once per session for the other bird. The effects of chlordiazepoxide and d-amphetamine were assessed on this baseline of behavior suppressed by conditioned punishment. Chlordiazepoxide produced dose-related increases in the rate of punished responding, whereas d-amphetamine produced only decreases. In addition, chlordiazepoxide produced dose-related increases in response rate during the response-produced and response-independent stimulus presentations; d-amphetamine, however, only decreased responding during stimulus presentations.     

The effect of drugs on a fixed-ratio performance suppressed by a pre–time-out stimulus,

Pecking was reinforced by a fixed-ratio schedule with food, and responses during a red light produced a time out. If the bird did not respond during the red light, the light terminated and the bird could complete the FR schedule of positive reinforcement uninterrupted. The bird stopped responding during the red light sufficiently to avoid most of the possible time outs. In general, the pre–time-out stimulus suppressed responding more when the FR schedule was large than when it was small. The occurrence of the pre–time-out stimulus in the fixed ratio produced FR strain and extreme curvature atypical of normal fixed ratios of this size. Amobarbital, pentobarbital, chlorpromazine, and d-amphetamine injected when the FR performance was strained by the pre–time-out procedure produced marked increases in responding. The drug administration lowered the rate of responding only at larger doses; and then this occurred predominantly just after the injection.     

Schedules using noxious stimuli. II: low intensity electric shock as a discriminative stimulus

The presence or absence of pulses of low intensity electric shock was used as a discriminative stimulus to control responding under fixed ratio reinforcement in the squirrel monkey. Initially brief periods of nonreinforcement were lengthened only when discriminative control was evident. Discriminative control was studied by (1) varying the duration of nonreinforcement periods; (2) reversing the stimulus conditions correlated with reinforcement and nonreinforcement periods; and (3) determining the minimum shock intensity necessary to maintain discriminative control. Stimulus control was not reliably affected by d-amphetamine, chlorpromazine, or morphine. The discriminative control by pulses of low intensity electric shock was similar to that by other discriminative stimuli, except that the control developed slowly and was better when the pulsing shock was correlated with reinforcement than when correlated with nonreinforcement.     

Drug postulate of Eysenck in the rat

The present work is an attempt to investigate the Drug Postulate of Eysenck in the animal field. The Ss were 36 male Wistar rats. The extraversion measure used was animal ambulation in a low-frightening open-field. d-Amphetamine, reserpine and saline were administered before the extinction of a lever-press FR 25 schedule for food. The results show that reserpine produces a decrement in the resistance to extinction (RExt), while d-amphetamine produces a biphasic effect, increasing the RExt in high-ambulatory (extravert) rats and leaving the RExt of low-ambulatory (introvert) rats unaffected. Therefore, reserpine acted as a depressant drug, d-amphetamine as a stimulant drug and ambulation as extraversion.     

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

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

Choice based on separately established response tendencies: The effect of recency of reinforcement

The responding of pigeons was studied in a chamber with two adjacent keys that could each be lit with either a red or a green dot. Fixed-length trials were used, with pecking on positive trials reinforced by presenting food at the end of the trial. In each session the first 40 trials were one-key trials with one key lit on each trial, either red or green, and the next four trials were choice trials with both keys lit, one red and the other green. When blocks of sessions were presented in which all one-key trials were positive trials of a single color, choice responding gradually shifted to the color presented most recently during one-key trials. When all one-key trials were nonreinforced trials of a single color, responding on choice trials shifted toward the other color. When positive one-key trials of one color were intermingled with negative one-key trials of the other color, choice responding shifted exclusively to the reinforced color. These shifts in choice responding occurred even when responding on choice trials was never reinforced, and were viewed as based on separate response tendencies for pecking red and pecking green built up during one-key trials.     

Spaced responding in multiple DRL schedules

Rats were able to adjust to two different temporal requirements within several multiple DRL schedules of reinforcement, and a slight induction between pairs of components was found. Initial administration of dl-amphetamine differentially disrupted spaced responding in the components of a multiple DRL 36 DRL 18 schedule, but did not eliminate discrimination between the components. After maximum drug effects, the continued administration of dl-amphetamine was accompanied by a progressive recovery of the behavior towards the characteristics of saline control.     

Stimulus generalization of the effects of punishment

Three pigeons were trained to respond to seven spectral stimulus values ranging from 490 to 610 mμ and displayed in random order on a response key. After response rates had equalized to these values, a brief electric shock was administered when the subject (S) responded to the central value (550 mμ) while positive reinforcement for all values was maintained. Initially, there was broad generalization of the resulting depression in response rate, but the gradients grew steeper in the course of testing. When punishment was discontinued, the rates to all values recovered, and equal responding to all stimuli was reattained by two of the Ss. Stimulus control over the effects of punishment was clearly demonstrated in the form of a generalization gradient; this probably resulted from the combined effects of generalization of the depression associated with punishment and discrimination between the punished value and neutral stimuli.     

Contrast and induction in rats on multiple schedules

Eight rats were trained on a variable-interval schedule in the presence of a light (Phase I). Responding was then extinguished in the presence of darkness that alternated with the light (Phase II). Reinforcement was then introduced in the presence of darkness (Phase III). Several rats were then returned to the condition of Phase II (Phase IV) and then to that of Phase III (Phase V). The responding of most rats showed clear behavioral contrast in Phase II—i.e., an increase in responding in the presence of the light. When, for three rats, Phase III was introduced early after the occurrence of positive contrast, either positive induction occurred, i.e., an increase in responding in the presence of the light, or there was little change. Negative contrast did not occur. It was further shown that positive contrast dissipates over time, thus replicating a result previously obtained with pigeons and that the positive induction effect seems also to dissipate over time. The introduction of reinforcement in the presence of darkness (Phases III and V) after the dissipation of positive contrast seemed to have little consistent effect.     

Effects of promazine, chlorpromazine, d-amphetamine, and pentobarbital on treadle pressing by pigeons under a signalled shock-postponement schedule.

The effects of promazine on treadle pressing to postpone the presentation of electric shock were studied in three pigeons. The effects of chlorpromazine, d-amphetamine, and pentobarbital were studied in two of these pigeons. Each treadle press postponed electric shock for 20 sec and presentation of a preshock stimulus for 14 sec. Selected doses of both promazine and chlorpromazine increased the rates of treadle pressing in all birds. The response-rate increases produced by promazine and chlorpromazine were due to increased conditional probabilities of treadle pressing both before and during the preshock stimulus. d-Amphetamine (1 and 3 mg/kg) slightly increased responding in one of the birds, but not to the extent that promazine or chlorpromazine did. In the other bird, the 10 mg/kg dose of d-amphetamine increased shock rate but did not change response rate. Some doses of d-amphetamine increased the conditional probabilities of responding both in the absence of the preshock signal and during the preshock signal in both birds. Pentobarbital only decreased response rates and increased shock rates.     

Characteristics of forgetting functions in delayed matching to sample

Performance of pigeons in delayed matching-to-sample procedures was measured in terms of an index of discriminability derived from the difference between logarithms of ratios of choice responses to comparison stimuli following the different sample stimuli. Forgetting functions that plotted discriminability as a function of delay-interval duration were well described by a simple negative exponential function with two parameters, one describing initial discriminability of sample stimuli at zero delay (log d₀) and the other describing rate of decrement in discriminability with increasing delay-interval duration (b). With the difference between wavelength values of the comparison stimuli held constant, a large difference between wavelengths of the sample stimuli resulted in a higher log d₀ value than that for a small difference between sample stimuli, without changing the rate of decrement in discriminability, b. An increase in the fixed-ratio requirement for sample-key responding produced an increase in log d₀ without affecting b, and interpolation of ambient illumination in the delay interval increased b without influencing log d₀. Both parameters changed when intertrial-interval duration was varied. The result of variation in the point of interpolation of ambient illumination in the delay interval indicated that levels of discriminability at longer delays were independent of discriminability levels at earlier delays, consistent with the properties of the exponential function. Functions relating performance to delay-interval duration were suggested to have two characteristics: discriminability of the sample stimuli in the absence of a delay between the stimuli and the behavior they occasion, and rate of attenuation in discriminability with increasing delay-interval duration.     

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.     

Pigeons respond to produce periods in which rewards are independent of responding

Pecks by pigeons on a response key produced an ON state during which intermittent rewards were freely available, i.e., independently of responding. Pecks during the ON state caused it to remain ON. If no pecks occurred, the state changed to OFF—the key color changed—and rewards were not presented. The state remained OFF until the next response. Thus, responses controlled the state in the chamber but did not cause immediate reinforcement. Four dimensions of the schedule were varied: the rates of response-independent rewards during ON; the duration of ON produced by each peck; the pattern of rewards during ON; and the presence vs absence of exteroceptive cues during ON and OFF. The results showed that rates of responding were primarily controlled by the duration of ON produced by each response. When each response caused a long period of ON, pecks occurred infrequently; when each response caused a brief period of ON, pecks were frequent.     

The role of the response-reinforcer contingency in negative automaintenance

When a response key is briefly illuminated before a grain reinforcer is presented, key pecking is reliably developed and maintained in pigeons, even if pecking prevents reinforcement (negative automaintenance). This experiment demonstrated that pigeons are sensitive to a negative response-reinforcer contingency, even though it does not eliminate responding. Within individual pigeons, two kinds of trials were compared: red key trials, in which reinforcement was negatively contingent on responding, and white key trials, in which reinforcement was unrelated to responding. Reinforcement frequency in non-contingent trials was yoked to the obtained reinforcement frequency in negatively contingent trials. All eight pigeons pecked substantially more on the non-contingent key than on the negative key, and preferred the non-contingent key to the negative key on occasional “choice” trials where both were presented together. When the stimuli correlated with the two conditions were reversed, the pigeons' behavior also shifted. These response differences are taken as evidence that pigeons are sensitive to the negative response-reinforcer contingency.     

Selective antagonism of the rate-decreasing effect of d-amphetamine by chlorpromazine in a repeated-acquisition task.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. When d-amphetamine was administered alone, the overall response rate decreased and the percent errors increased with increasing doses. When a small dose of chlorpromazine, which was ineffective when given alone, was administered in combination with d-amphetamine, the rate-decreasing effect was antagonized. The antagonism was selective, however, in that the error-increasing effect of d-amphetamine was augmented by chlorpromazine. The nature of the joint effect of the two drugs thus depended on the behavioral measure: rate vs. accuracy.     

Response-dependent shock in second-order fixed-ratio schedules of food presentation

Three pigeons key pecked under second-order schedules in which the completion of two successive fixed-ratio 50 components constituted a reinforcement cycle. Tandem, chained, and brief-stimulus second-order schedules were studied when completion of the initial fixed-ratio 50 component delivered brief intense electric shock in every nth reinforcement cycle and n assumed values between one and nine. During sessions without shock, the brief-stimulus (unpaired with food) schedule generated higher rates of responding in the initial component than did the tandem schedule. Electric shock engendered increased time to the fifth response and a repeated pause-run pattern of not responding and responding, particuuarly in the initial component, even with shock scheduled in every ninth reinforcement cycle. The results were consistent with those reported for shock of a shorter duration scheduled in every reinforcement cycle. The overall rate of responding decreased as a function of increasing shock density and was lower in brief-stimulus than in tandem schedules.     

Behavioral contrast as a function of the duration of an immediately preceding period of extinction

For four pigeons key-peck responding was reinforced on a variable-interval reinforcement schedule in the presence of a vertical white line. When response rates had stabilized a horizontal white line was introduced, in the presence of which reinforcement was not available (extinction). The horizontal line was presented once per session, immediately before the vertical line was presented. The duration of the horizontal line varied randomly from session to session, being either 0 sec (i.e., no presentation), 10 sec, 30 sec, 2 min, 10 min, 40 min, or 120 min. When the horizontal line was present for more than 0 sec, behavioral contrast was obtained in the presence of the following vertical line. Contrast increased with increasing durations of the horizontal line, asymptoting when the horizontal line was present for 40 min.     

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.