Current Topics in Animal Learning

Brain, Emotion, and Cognition

Lawrence Dachowski, Charles F. Flaherty

• Publisher: Psychology Press
• Year: 2013
• ISBN:
  9781134748938
• Edition: 1
• Topic: Psychologie
• Subtopic: Geschichte & Theorie in der Psychologie

This book, based on the Flowerree Mardi Gras Symposium at Tulane University, juxtaposes contemporary research and theory from several areas of animal learning -- learning theory, comparative cognition, animal models of human behavior, and functional neurology. Investigators pursuing these different routes often work in isolation of progress being made in, what should be, related fields. This book will acquaint students and researchers with a variety of topics, ordinarily treated separately, in a way that will stimulate integrative thinking. Cognitive interpretations of animal learning are included, as well as recent developments in conditioning theory, physiological bases of learning, animal models of human behavior problems, and psychopharmacology.

1Memory Processes, ACTH, and Extinction Phenomena

Rick Richardson

Princeton University

David C. Riccio

Kent State University

That hormones can profoundly influence a number of basic behaviors is now well established. In addition to the prenatal organizational effects of hormones on the structure and function of the central nervous system (Carlson, 1981) a wide variety of activational influences can be found. For example, feeding, reproduction (Leshner, 1978; chapters 2 & 5), and maternal behavior (Rosenblatt, 1987) are all greatly affected by the animal’s hormonal state. Initiation and maintenance of each of these behaviors seems to be controlled, at least in part, by one hormone or another. Until relatively recently, the role of hormones in more cognitive activities has received less emphasis. However, there is accumulating evidence that certain hormones influence various cognitive functions including attention, learning, and memory (Beckwith & Sandman, 1978; deWeid, 1970; McGaugh, 1983). One hormone that has been of particular interest in this regard is adrenocorticotropic hormone (ACTH). The effect of this hormone on learning and memory has attracted considerable attention in the last two decades (Bohus & deWeid, 1981; Riccio & Concannon, 1981).

The influence of ACTH on learning has been demonstrated in at least two very different ways. For example, some investigators have shown that exogenous ACTH influences the strength of learning while others have shown that exogenous ACTH can function as an internal cue to mediate learning across different environmental situations. As an example of the first approach, Gold and van Buskirk (1976) found that post-training injections of ACTH had a dose-dependent effect on the learning of both passive and active avoidance in rats. That is, post-training injections of low doses of ACTH enhanced the learning of these responses while high doses had the opposite effect. Gold and van Buskirk (1976) suggested that post-training ACTH influenced learning by modifying memory consolidation. Other investigators have replicated these results although some have suggested that the amnestic effect produced by high doses of ACTH immediately following training is due to state-dependent learning rather than modification of memory storage processes (Izquierdo & Dias, 1983).

An example of a situation where exogenous ACTH serves as a mediating cue to establish learning to neutral environmental cues is provided by a study by Concannon, Riccio, Maloney, and McKelvey (1980). These investigators employed a “redintegration” procedure to show that animals could use the internal state produced by high levels of ACTH to associate temporally separate events. In this procedure, release of endogenous ACTH was induced in Phase 1 by subjecting rats to the stress of repeated shocks in an unpainted wooden box. Control animals were merely exposed to the chamber without being shocked. On the following day (Phase 2), all animals were exposed to the black compartment of a black-white shuttle box. Prior to being placed in the black compartment some subjects were given ACTH and others saline. Half of the animals in each drug condition had been previously shocked while the other half had not. The third phase consisted of a test for fear of the black compartment. The major outcome of this study was that only those animals that had been shocked and given ACTH prior to being exposed to the distinctive cues exhibited fear (as measured by avoidance of the black chamber). Concannon et al. (1980, p. 977) offered the following interpretation for their results: “It appears that an appropriate internal state can redintegrate a previous emotional response which becomes associated with contemporaneous external stimuli.” That is, the high levels of ACTH present at the time of these two events allowed animals to associate exposure to the black compartment with shock—even though the two had never occurred together! This paradigm can also be viewed as a variant of higher-order Pavlovian conditioning, but with the important distinction that the transfer of fear is based upon the role of an interoceptive state (ACTH and correlated stimuli), rather than an exteroceptive signal, as the first order CS. Whatever accounts for this effect, endogenous opiate systems appear to be at least partly involved as injections of naltrexone 5 min prior to the ACTH injection completely blocked acquisition of this fear (Concannon et al., 1980; also see DeVito & Brush, 1984).

In addition to influencing learning, exogenous ACTH also appears to affect memory processes. For example, exogenous ACTH, and related peptide fragments, are effective in alleviating retention deficits produced by a wide variety of experimental treatments. Rigter, Van Riezcn, and dcWeid (1974) demonstrated that CO₂-induced retrograde amnesia (RA) for a passive avoidance task could be attenuated by injecting ACTH4.10 shortly prior to the retention test. Similarly, Mactutus, Smith, and Riccio (1980) demonstrated the alleviation of hypothermia-induced RA by pretest injections of ACTH. Another situation where exogenous ACTH is effective in alleviating retention deficits comes from the work of Klein (1972) on the Kamin effect. Kamin and others (Kamin, 1957; Klein & Spear, 1970) have shown that subjects trained on an active avoidance task and then tested after an intermediate retention interval (1–6 hr) perform more poorly than subjects tested cither immediately or 24 hr after training. However, Klein (1972) found that animals tested after an intermediate retention interval did not show the usual retention loss if they were injected with ACTH shortly prior to the test session. Clearly, exogenous ACTH is an effective treatment in alleviating retention deficits in a number of situations (also see Haroutunian & Riccio, 1979).

But perhaps the best known work concerning the effects of ACTH on learning and memory is the extensive series of studies by deWeid and his colleagues on the extinction of avoidance behaviors (Bohus & deWeid, 1966, 1981; deWeid, 1966). Typically, it has been reported that animals given ACTH prior to a test session are more resistant to extinction than are subjects given only the vehicle. That is, animals given ACTH prior to an extinction session continue to make the conditioned avoidance response longer than do controls. For example, deWeid (1966) trained rats on either an active avoidance task or a pole-jumping procedure. After reaching the training criterion animals were given one of a variety of treatments. For our purposes the important groups were those given ACTH or the vehicle. During subsequent extinction trials, animals given ACTH (either ACTH _1-39 or ACTH _1-10) continued to respond at a higher rate than animals given just the vehicle. These effects of exogenous ACTH on rate of extinction of the avoidance response are not due to alterations of motor activity per se, but appear to be due to some central effect. DeWeid and his colleagues have continued this line of research during the last two decades and have examined the effects of many different variables on hormonal influences on learning/memory (Bohus & deWeid, 1981).

From this extensive body of work several different mechanisms have been proposed to explain the influence of ACTH on learning/memory. A partial summary of these mechanisms include the notions that ACTH influences attentional processes (Mirsky & Orren, 1977), trial-to-trial memory (deWeid & Bohus, 1966), memory consolidation (Gold & Delanoy, 1981) or memory retrieval (Klein, 1972; Riccio & Concannon, 1981), the “motivational significance of environmental cues” (Bohus & deWeid, 1981), or that ACTH may be an attribute of memory (Bohus, 1982). Given the variety of reported effects of ACTH on learning and memory it is unlikely, as noted by Bohus and deWeid (1981), that any single explanation can account for them all. In the present chapter, however, we would like to focus on a series of experiments that were done from the perspective that ACTH (and concomitant internal changes) can be an integral component of memory.

A number of theorists have suggested that memory is best conceptualized as being comprised of many independent attributes (Spear, 1978; Underwood, 1969). This idea has proven to be quite fruitful in other areas of our work (e.g., experimentally-induced amnesia) so we decided to try to apply it to extinction. According to this view, memory consists of many different attributes, one of which is the internal state of the organism at the time of training. Furthermore, retrieval of a memory is, as stated by Spear and Mueller (1984, p. 117), “. . . governed by this simple, ancient principle; The more similar the circumstances are that comprise the episode originally learned and those present when memory retrieval is required, the greater the retention.” Therefore, if during training the animal experiences high levels of ACTH, then retention will be enhanced if the animal also experiences high levels of ACTH at test. The familiar analogy used to describe this relationship involves generalization decrement. That is, if an animal is trained on some task its performance becomes degraded as the testing cues become increasingly dissimilar to those used in training. With respect to memory processes, the argument would be that retention is a direct function of the similarity of the cues present at test to those originally encoded. As the two sets of cues become more similar retention increases.

The idea that ACTH is a component of memory predicts that administration of ACTH will have quite different effects depending on when it is given. Under some circumstances, the effects of the hormone should be reflected in better performance of the original learned behavior. Consistent with this view, there is substantial evidence that exogenous ACTH prolongs the persistence during extinction of both active avoidance responding (deWeid, 1966) and conditioned taste aversions (Levine, Smotherman, & Hennesy, 1977). Also, as noted, administration of ACTH prior to testing can ameliorate retention deficits produced by amnestic agents (Keyes, 1974; Mactutus, Smith, & Riccio, 1980). On the other hand, the functional effect of enhanced memory retrieval following ACTH administration should be quite different if the experimental paradigm were re-arranged. For example, enhancing retention of the target memory during an extinction session should make that memory more susceptible to the effects of the extinction treatment. This, of course, would lead to poorer performance on a subsequent retention test. These predictions concerning the effects of exogenous ACTH on extinction of avoidance responding were tested in a series of experiments in our laboratory.

RECOVERY OF AN EXTINGUISHED AVOIDANCE RESPONSE BY ACTH

The question addressed in these initial experiments was whether injections of ACTH at the time of testing would be effective in alleviating performance decrements induced by a prior extinction session. That is, would animals that had been trained to make an avoidance response and then had that response extinguished, show stronger responding when given ACTH at testing?

As noted earlier, pre-test injections of ACTH have been found to alleviate retention deficits in a variety of situations. Although performance decrements produced by an extinction treatment are not typically thought of as being “retention” phenomena, both stimulus sampling theory (Estes, 1955) and empirical data suggest some commonalities between performance decrements resulting from manipulations involving extinction or retention loss. For example, noncontingent footshock is often used to alleviate retention deficits produced by experimentally-induced retrograde amnesia (Mactutus, Ferek, & Riccio, 1980; Miller & Springer, 1972), and it also has been shown to be effective in producing substantial recovery of an extinguished conditioned emotional response (Rescorla & Heth, 1975). However, regardless of whether performance decrements produced by extinction are viewed as “retention” losses or not, pretest injections of ACTH would increase the similarity between training and testing. The closer correspondence of stimulus conditions should promote greater retrieval which in turn should enhance performance. The focus on recovery of the extinguished memory, rather than resistance to extinction, is of course analogous to our work on the reversal of memory loss from retrograde amnesia (Mactutus, Ferek, & Riccio, 1980) or from infantile amnesia (Riccio & Haroutunian, 1979).

Another issue examined in this experiment concerned the possible time-dependent nature of any effect ACTH might have on retention. As noted earlier, administration of particular hormones (e.g., ACTH or epinephrine) immediately after training can have a profound impact on the animal’s subsequent performance. However, it is typically the case that if a delay is introduced between training and hormone delivery then the hormone has no effect (Gold & van Buskirk, 1976). In the same fashion, it would seem that exogenous ACTH would influence memory retrieval only for as long as the hormone, or its internal concomitants, are present. Therefore, introducing a delay between ACTH injection and testing should lessen the effectiveness of this treatment as a reminder. Indeed, Mactutus, Smith, and Riccio (1980) found that exogenous ACTH alleviated experimentally induced amnesia if the animal was tested 0.5 hr, but not 24 hr, after hormone administration. Furthermore, it should be noted that deWeid (1966) used a long-lasting form of the peptide (containing zinc phosphate) in his experiment described earlier and even concluded “Apparently, the chronic presence of the peptide is obligatory to exert the effect” (pp. 30–31).

Passive Avoidance

In this experiment, adult male rats were trained to fear the black compartment of a black-white shuttle box (Richardson, Riccio, & Devine, 1984; Experiment 4). A Pavlovian differential conditioning procedure was used to condition fear. In this procedure animals were confined to the black side for two separate 2 min periods during which 12 inescapable footshocks were administered. All animals received an equivalent amount of exposure to the white compartment where no shock was given. A passive avoidance procedure was used to assess retention. That is, animals were placed in the white side of the shuttle box and the time taken to enter the black compartment was recorded. In this test, long latencies to enter the black compartment are indicative of good retention.

Twenty-four hours following training 3 groups of animals were given a 90 s nonreinforced exposure to the black compartment (i.e., an extinction exposure). Subjects in a fourth group did not receive any treatment on this day. Seventy-two hours after training all animals were tested for fear of the black compartment. Of the three groups that were extinguished, one was given 4 IU of ACTH (Acthar gel, Armour Pharmaceutical) and another was given the same volume of physiological saline shortly prior (15–20 min) to test. Subjects in the third extinguished group were injected with ACTH 24 hr prior to test.

As can be seen in Figure 1.1, extinguished animals given saline prior to test were quite different from the retention controls (i.e., trained but unextinguished animals). The extended nonreinforced exposure was quite effective in reducing the conditioned fear of the black compartment. Unlike the cxtinguished animals given saline, subjects given ACTH prior to testing were not different from the retention controls. Those rats given ACTH prior to the test were just as fearful of the black compartment as w...

Table of contents

• Front Cover
• Title Page
• Copyright
• Contents
• Contributors
• Preface
• 1. Memory Processes, ACTH, and Extinction Phenomena
• 2. Context and Retrieval in Extinction and in Other Examples of Interference in Simple Associative Learning
• 3. Event Revaluation Procedures and Associative Structures in Pavlovian Conditioning
• 4. Expression of Learning
• 5. Memory Strategies in Pigeons
• 6. The Acquisition of Concrete and Abstract Categories in Pigeons
• 7. Comparative Cognition: Processing of Serial Order and Serial Pattern
• 8. Parallels Between the Behavioral Effects of Dimethoxy-beta-carboline (DMCM) and Conditioned Fear Stimuli
• 9. Incentive Contrast and Selected Animal Models of Anxiety
• 10. Consummatory Incentive Contrast: Experimental Design Relationships and Deprivation Effects
• 11. Multiple Memory Systems in the Mammalian Brain Involved in Classical Conditioning
• 12. Contribution of the Amygdala and Anatomically-Related Structures to the Acquisition and Expression of Aversively Conditioned Responses
• 13. Animal Models of Alzheimer’s Disease: Role of Hippocampal Cholinergic Systems in Working Memory
• 14. Brain, Emotion, and Cognition: An Overview
• Author Index
• Subject Index