Contrast and inhibition in discrimination learning by the pigeon: Analysis through drug effects

In a series of four experiments, pigeons were trained on either an easy, red/green discrimination with or without a penalty for errors, or a more difficult left/right discrimination with penalty. Some groups of birds were injected with chlorpromazine or desipramine prior to acquisition sessions or to sessions following learning of the discrimination. Drug injection caused substantial impairment of acquisition or retention of the left/right discrimination alone, whereas in all discriminations the behavioral contrast effect was abolished. The results suggest that inhibition of errors depends upon the difficulty of discrimination and the presence of a penalty procedure, and determines both contrast in the saline-injected groups and the extent of impairment in the drug-injected groups.     

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.     

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.     

Cholinergic rebound after chlorpromazine exacerbates lithium muscarinic-induced limbic seizures in rats: implications for psychiatric treatment.

When lithium serum levels were within the (human) therapeutic range, young and old adult male and female rats (housed singly or in groups) all displayed faster limbic seizure onset times in response to a muscarinic cholinergic agonist (pilocarpine 20 mg/kg) if a single systemic dosage of chlorpromazine was injected 24 hours previously. The effect was comparable to injecting an additional 10 mg/kg of pilocarpine. These results strongly suggest that cholinergic rebound from chlorpromazine administrations during lithium treatment could facilitate subclinical electrical lability and very localized neuronal necrosis within the limbic system of clinical patients, resulting in normalization of psychiatric symptoms.     

Effects of chlorpromazine on lateralization,cued reaction time,and dichotic listening

In a double-blind cross-over design sixteen subjects took 50 mg of chlorpromazine or placebo in tablet form 2 hours prior to completing a dichotic listening and simple reaction time task with and without warnings. In the simple reaction time task, blocks of 80 stimuli were presented to each ear with and without warning cue under drug and placebo conditions. On the dichotic listening task the expected right ear advantage for reporting digits was obtained. While the drug had no main effect on the number of errors, there were more trials on which an ear advantage was present than in the placebo condition. In the reaction time task there were main effects of drug, warning cue and foreperiod: warnings facilitated reaction; chlorpromazine retarded reaction; and reaction times were most facilitated by warning foreperiods in excess of 1200ms. Several findings were of interest: On uncued trials, with placebo, right ear responses were faster than those for stimuli presented to the left ear. Drug also interacted with foreperiod duration. These results were interpreted in the light of Tucker and Williamson’s (1984) review of the role of Pribram and McGuinness’s Arousal and Activation sytems in lateralized behavior.     

Effects of chlorpromazine on lateralization, cued reaction time, and dichotic listening

In a double-blind cross-over design sixteen subjects took 50 mg of chlorpromazine or placebo in tablet form 2 hours prior to completing a dichotic listening and simple reaction time task with and without warnings. In the simple reaction time task, blocks of 80 stimuli were presented to each ear with and without warning cue under drug and placebo conditions. On the dichotic listening task the expected right ear advantage for reporting digits was obtained. While the drug had no main effect on the number of errors, there were more trials on which an ear advantage was present than in the placebo condition. In the reaction time task there were main effects of drug, warning cue and foreperiod: warnings facilitated reaction; chlorpromazine retarded reaction; and reaction times were most facilitated by warning foreperiods in excess of 1200ms. Several findings were of interest: On uncued trials, with placebo, right ear responses were faster than those for stimuli presented to the left ear. Drug also interacted with foreperiod duration. These results were interpreted in the light of Tucker and Williamson’s (1984) review of the role of Pribram and McGuinness’s Arousal and Activation sytems in lateralized behavior.     

The suppressing effect of chlorpromazine treatment on alimentary-social differentiation in amygdala dogs

Experiments were performed on dogs with bilateral electrolytic damage of dorso-medial amygdala. Before the operation dogs were trained in alimentary-social reward differentiation. It consisted in conditioning of instrumental responses of either right or left foreleg to two different tones respectively. Chlorpromazine was injected intramuscularly in 1,5 mg/kg dose during four consecutive days, beginning at third to fifth week after the operation. Amygdala damage produced significant deterioration of the instrumental performance both reinforced by food and by social-sensory rewards. Chlorpromazine produced further dramatic decrease of performance of both responses. It was concluded that chlorpromazine exerts a suppressing effect on motivated behavior reinforced by positive rewards in amygdala dogs. As the effect of chlorpromazine and medial amygdalar damage are summated it may be suggested that the deficit of medial amygdala neurons impairs similar neurochemical mechanisms, (probably dopaminergic and α-adrenergic transmission) as does chlorpromazine.     

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.     

Gender differences in the pathway from adverse life events to adolescent emotional and behavioural problems via negative cognitive errors

The aim of this study was to test for gender differences in how negative cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and personalizing) mediate the association between adverse life events and adolescents’ emotional and behavioural problems (measured with the Strengths and Difficulties Questionnaire). The sample consisted of 202 boys and 227 girls (aged 11–15 years) from three state secondary schools in disadvantaged areas in one county in the South East of England. Control variables were age, ethnicity, special educational needs, exclusion history, family structure, family socio‐economic disadvantage, and verbal cognitive ability. Adverse life events were measured with Tiet et al.'s (1998) Adverse Life Events Scale. For both genders, we assumed a pathway from adverse life events to emotional and behavioural problems via cognitive errors. We found no gender differences in life adversity, cognitive errors, total difficulties, peer problems, or hyperactivity. In both boys and girls, even after adjustment for controls, cognitive errors were related to total difficulties and emotional symptoms, and life adversity was related to total difficulties and conduct problems. The life adversity/conduct problems association was not explained by negative cognitive errors in either gender. However, we found gender differences in how adversity and cognitive errors produced hyperactivity and internalizing problems. In particular, life adversity was not related, after adjustment for controls, to hyperactivity in girls and to peer problems and emotional symptoms in boys. Cognitive errors fully mediated the effect of life adversity on hyperactivity in boys and on peer and emotional problems in girls.     

Pharmacological effects on lateralized behavior

Sixteen student volunteers were administered a placebo and 50 mg. of chlorpromazine in tablet form, on separate occasions, two hours before testing. The three tests measured dichotic listening performance, lateral eye movements while answering questions about spatial location and verbal meaning, and lateralized facial expression while relating pleasant and unpleasant life incidents. Results showed that chlorpromazine increased the number of trials showing an ear advantage in dichotic listening. Chlorpromazine reduced lateral and increased vertical eye movements in response to the questions about spatial location and verbal meaning. Under the placebo both negative and positive emotions were expressed more in the left face. Although chlorpromazine did not affect this lateralization of negative emotions, the expression of positive emotions occurred equally often on the two sides of the face under chlorpromazine. Results may be related to an effect of chlorpromazine on the asymmetrical dopamine pathways of the brain. It is suggested that the findings may be related to a left hemisphere deficit in schizophrenia.     

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.     

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.     

Quantification of the effects of chlorpromazine on performance under delayed matching to sample in pigeons.

The effects of four doses of chlorpromazine (dose range 0.5 to 12.5 mg/kg) on performance under a delayed matching-to-sample procedure in pigeons was investigated, using the exponential model of memory (White, 1985). Performance was measured using a bias-free measure of discriminability, log d (Davison & Tustin, 1978), and negative exponential functions were fitted to individual-subject and group data at each dose level. A decrease in matching accuracy was found to be caused by an increase in the rate of forgetting, b, and a decrease in the initial discriminability, log d0. Changes in rate of forgetting and discriminability occurred at doses that had no statistically significant effect on response latency. The exponential model of memory accounted well for the data and provided a useful way of quantifying the effects of chlorpromazine on the processes involved in delayed matching-to-sample performance.     

Antagonism of a behavioral effect of d-amphetamine by chlorpromazine in the pigeon

A dose of d-amphetamine which completely suppressed all responding was administered to each of five pigeons under an FR 30 schedule. When the pigeons were treated with chlorpromazine after 45 min or more, responding was restored. When d-amphetamine and chlorpromazine were administered simultaneously to three other pigeons, responding was better maintained than after d-amphetamine alone. This study confirms a previous finding that chlorpromazine can antagonize the rate-decreasing effect of d-amphetamine.     

樟柳碱所致学习和记忆障碍动物模型的探讨

本实验采用水迷津法、步下法和步入法,用樟柳碱制备学习和记忆障碍的动物模型。结果表明,樟柳碱(10毫克/公斤)可使小鼠引起学习障碍,其表现为通过水迷津全程的时间延长,而且小鼠进入盲路的错误次数明显增多。樟柳碱(10毫克/公斤)可使小鼠引起记忆障碍,在樟柳碱的影响下,小鼠步下平台或步入暗箱的潜伏期明显缩短,并使它们的错误次数增多。本实验结果进一步表明,测定小鼠的记忆障碍,步入法似乎比步下法更为敏感。     

SUBJECTIVE ESTIMATION OF DRUG-INDUCED CHANGES IN ACTIVATION LEVEL

For comparative evaluation of the subjective effects of 50 mg chlorpromazine, 0.10 g amobarbital and 10 mg amphetamine (phenopromine. sulf.) two types of formalized rating procedures—a verbal check list and graphic rating scales—were administered to 187 university students. Repeated self-ratings were performed 45, 90 and 180 minutes after oral intake. By the check-list method the expected difference between amphetamine and chlorpromazine was significantly established in all the three ratings. Only in the 45-minute rating was a significant difference obtained between amobarbital and amphetamine. The graphic rating scales were clearly less efficient as judged from the greater proportion reporting 'no change'.     

Epinephrine modulates long-term retention of an aversively motivated discrimination

These experiments examined the effects of post-training epinephrine (Epi) on retention of an aversively motivated discrimination task. Male CFW mice were trained to escape from footshock by entering one of two alleys of a Y-maze. On a 24-h retention test (six trials) the correct alley was reversed. The findings of Experiment 1 indicate that errors on the discrimination reversal varied directly with number of trials (criterion of 0, 3, or 6 successive correct choices) on the original training. These findings indicate that errors on discrimination reversal training provide a sensitive index of retention of the original training. In Experiment 2, mice were trained to a criterion of three successive correct choices and were given post-training injections of saline or Epi (0.1, 0.3, or 1.0 mg/kg ip). On a 24-h discrimination reversal test mice given the low doses of Epi made more errors than did saline controls while mice given the high dose made fewer errors. In Experiment 3, mice trained as in Exp 2 received post-training saline or Epi (0.3 or 1.0 mg/kg) and were tested for retention either 1 week or 1 month later. At each retention interval, performance was comparable to that found with a 24-h retention interval. The findings provide additional evidence that post-training Epi produces long-lasting dose-dependent modulating effects on memory storage.     

Beyond hypercorrection: remembering corrective feedback for low-confidence errors*

Correcting errors based on corrective feedback is essential to successful learning. Previous studies have found that corrections to high-confidence errors are better remembered than low-confidence errors (the hypercorrection effect). The aim of this study was to investigate whether corrections to low-confidence errors can also be successfully retained in some cases. Participants completed an initial multiple-choice test consisting of control, trick and easy general-knowledge questions, rated their confidence after answering each question, and then received immediate corrective feedback. After a short delay, they were given a cued-recall test consisting of the same questions. In two experiments, we found high-confidence errors to control questions were better corrected on the second test compared to low-confidence errors – the typical hypercorrection effect. However, low-confidence errors to trick questions were just as likely to be corrected as high-confidence errors. Most surprisingly, we found that memory for the feedback and original responses, not confidence or surprise, were significant predictors of error correction. We conclude that for some types of material, there is an effortful process of elaboration and problem solving prior to making low-confidence errors that facilitates memory of corrective feedback.     

The effect of task-relevant and irrelevant anxiety-provoking stimuli on response inhibition

The impact of anxiety-provoking stimuli on the Sustained Attention to Response Task (SART; Robertson, Manly, Andrade, Baddeley, & Yiend, 1997), and response inhibition more generally, is currently unclear. Participants completed four SARTs embedded with picture stimuli of two levels of emotion (negative or neutral) and two levels of task-relevance (predictive or non-predictive of imminent No-Go stimuli). Negative pictures had a small but detectable adverse effect on performance regardless of their task-relevance. Overall, response times and rates of commission errors were more dependent upon the predictive value (relevance) of the pictures than their attention-capturing nature (i.e., negative valence). The findings raise doubt over whether anxiety improves response inhibition, and also lend support to a response strategy perspective of SART performance, as opposed to a mindlessness or mind-wandering explanation.     

Amphetamine disrupts both working and reference memories of rats trained in a radial maze

To assess the effects of amphetamine on working and reference memory rats were trained on a 12-arm radial maze with six arms baited and six arms unbaited until stable performance was achieved. Administration of 2.0 mg/kg d-amphetamine sulfate increased both working and reference memory errors, but only if a 5-min delay was imposed after three successful choices. With no delay this dose had no reliable effect on either working or reference memory. Lower doses (0.5 or 1.0 mg/kg) were ineffective even when a delay was imposed during the test. We suggest that amphetamine heightens arousal, which disrupts accurate retention when the rat's attention to the relevant cues is interrupted, as during a brief delay. Alternative explanations are discussed.