Modern science has developed to such a point that there are myriad research areas, dark corners as well as bright little chambers, that are penetrated only by a knowledgeable few who happen to be working in a given field – the specialists. I would not be surprised, then, to discover that most of my colleagues, whether they label themselves psychologists, psychobiologists, behavioral scientists, or neuroscientists, do not know what “latent inhibition” is, or at best confuse the term with older research areas that are indeed its distant cousins – latent learning and conditioned inhibition. It is for these readers that I begin this treatise with a definition, as simple as it may be.

“Latent inhibition” is defined by three characteristics. One is concerned with conditions for producing it, the second with the conditions for measuring the effect, and the third with the direction of the differences between groups. More specifically, latent inhibition is the detrimental effect of passive, nonreinforced preexposure of a stimulus on the subsequent ability of an organism to form new associations to that stimulus. To demonstrate latent inhibition, one must preexpose one group of subjects to the stimulus of interest, while not giving such stimulus preexposure to a control group. In the test phase, both groups must learn to form an association between that stimulus and a new event. When the stimulus-preexposed group learns the new association to that stimulus more poorly than does the control group, we say that latent inhibition has been demonstrated.

In general, the effects of organismic variables have not been subjects of investigation in regard to latent inhibition. The few exceptions include the variables of age, sex, and handling, with the former receiving the greatest attention by far. These areas are represented by a small number of experimental investigations, and some conclusions may be reached from the controlled comparisons. In addition, however, there is a body of information that is derivable from the fact that experiments on latent inhibition have been performed in a variety of species. It is therefore possible to examine, between experiments, effects that, with considerable caution, may be attributable to species differences. Prudence is dictated by the fact that across studies there is almost complete confounding of species and testing procedures.

Age

Only two studies have looked at the effect of age on latent inhibition within the conditioned suppression paradigm (Cone, 1974; Wilson & Riccio, 1973). This, of course, is not surprising, because the basic technique, whether tube licking or bar pressing, requires a relatively mature motor system. Other procedures, such as odor preference, are more amenable to dealing with the inherent problems of testing immature organisms.

In a sketchy report that is difficult to evaluate, Cone (1974) reported an age-related latent inhibition effect in a one-trial conditioned suppression test. With rats that ranged in age from 30 to 365 days, all groups showed latent inhibition to a light CS, except the 90–120 day-old group.

In general, conditioned attention theory, CAT (Lubow, Schnur, & Rifkin, 1976; Lubow, Weiner, & Schnur, 1981), states that nonreinforced preexposure to a stimulus retards subsequent conditioning to that stimulus because during such preexposure the animal learns not to attend to it. The theory is based on the use of attention as a hypothetical construct, with the characteristics of a Pavlovian response, and on the specification of reinforcement conditions that modify attention.

The assumption that changes in attention to stimuli are a function of reinforcement conditions may be traced to Lashley (1929) and Krechevsky (1932). Likewise, Lawrence (1949) suggested that the “acquired distinctiveness of cues” might be a gradual learning process subject to traditional analysis. In more recent theorizing, changes in attention as a function of reinforcement conditions have been emphasized by Mackintosh (1975), Frey and Sears (1978), and Pearce and Hall (1980), as well as in the “selective attention” theories of Lovejoy (1968), Sutherland and Mackintosh (1971), Trabasso and Bower (1968), and Zeaman and House (1963).

In similarity to selective attention theories, CAT treats attention as a response, occurring on stimulus presentation, the probability of which is increased when it is followed by reinforcement and decreased when it is not reinforced. However, CAT differs from those theories in a number of important respects: the conditions specified for the changes in the attentional response; the mechanism postulated to govern such changes; and the course of these changes with repeated stimulus presentation.

Originally, this book was to have been organized such that a separate chapter would be devoted to each of the major paradigms within which latent inhibition had been demonstrated. Although such a categorization proved to be convenient for the initial organizing of the hundreds of published reports, it soon became clear that there was an absence of major differences in the latent inhibition phenomena that could be attributed to the type of testing procedure employed. Therefore, it was decided to present the empirical evidence for latent inhibition on the basis of manipulated variables, organismic variables, and variations across experiments. It is, of course, in this latter category that testing procedures are to be found. Procedures are placed at the head of the list, for two reasons: first, to present evidence that latent inhibition is indeed a ubiquitous phenomenon, found across a very wide range of testing procedures; second, by accomplishing the preceding, to avoid, in subsequent sections, the necessity of repetitiously labeling the experimental procedures for each point that is made.

Before identifying those paradigms in which latent inhibition has been investigated, two general comments are in order, one concerning the number of stages in the procedure, and the second concerning the problem of differentiating the conditioned response (CR) to the target stimulus in the test from the unconditioned response (UR) to that stimulus.

Although conditioned attention theory was developed specifically to account for latent inhibition effects, it is also relevant to other phenomena in the area of learning, particularly to those situations where the target stimulus is presented under conditions in which attention is diverted from it by competing stimuli, such as in blocking and overshadowing, or in which stimuli are presented repeatedly, as S1 in the preexposure phase of the learned helplessness paradigm, or S1–S2 in the first phase of sensory preconditioning. In regard to the first of these areas, Lubow, Weiner, and Schnur (1981) have already commented on the implications of conditioned attention theory for understanding blocking and overshadowing, as well as the feature positive effect. Similarly, in the second area, the relationships among CAT, learned helplessness, habituation, and sensory preconditioning have been explored. With the exception of learned helplessness, there is little to be added to the already published analysis, and the interested reader is referred to the original source (Lubow, Weiner, & Schnur, 1981). However, in regard to learned helplessness, new and important materials are available, enough to warrant a reconsideration of the relationship between latent inhibition and learned helplessness. In addition, a literature has recently developed on the relationship between latent inhibition, as it reflects normal attentional processes, and schizophrenia, often regarded as characterized by attentional dysfunction. These two topics, learned helplessness and schizophrenia, will be explored in the following two sections.

In the past, the extensive efforts to understand latent inhibition were directed at behavioral analyses of the phenomenon, the data from which we have discussed at some length in the previous chapters. More recently, however, a keen interest has developed in the neural substrates of latent inhibition. Although this certainly reflects a general trend in the experimental psychology of learning, the additional focus also can be partially explained by the relatively new interest in the area of attention among psychologists, as well as by the consensual opinion that latent inhibition reflects some aspect of attention (e.g., Lubow, Weiner, & Feldon, 1982). More specific manifestations of this direction can be seen in various attempts to evaluate the attentional deficits of schizophrenia by assessing impairments of latent inhibition (Baruch et al., 1988a,b; Lubow et al., 1987) and, at the same time, to explore the animal amphetamines model of schizophrenia by examining the effects of amphetamines as well as neuroleptics on latent inhibition in animals (e.g., Solomon et al., 1981; Solomon & Staton, 1982; Weiner et al., 1984; Weiner & Feldon, 1987; Weiner, Feldon, & Katz, 1987; Weiner, Lubow, & Feldon, 1981). In addition to these efforts, which will be described in the section on the effects of dopaminergic manipulations on latent inhibition, other brain systems have also been studied in this regard. These will be reviewed and discussed separately in sections on noradrenergic, serotonergic, cholinergic, septo-hippocampal, and opiate manipulations.

In the preceding chapter we developed and applied CAT to the data from latent inhibition studies with animals, but we ignored the data from experiments with human subjects. It will be recalled that these human studies present a pattern of results not entirely consistent with that obtained from lower organisms. To review, the major findings, presented in chapter 5, are as follows:

1. There are standard stimulus preexposure procedures that will produce latent inhibition in young children, but not in older children or adults.

2. If these same procedures are coupled with a masking task, then latent inhibition can be produced in older children and adults.

3. Nevertheless, there are some procedures (i.e., electrodermal conditioning, conditioned tasted aversion, and Ivanov-Smolensky conditioning) that may not require masking for the production of latent inhibition.

The last point will be dismissed, perhaps somewhat cavalierly, because of the difficulty in separating the unconditioned response to the CS (orienting or otherwise) from the conditioned response to the CS in the test phase. As a result, one cannot determine whether stimulus preexposure produces an artifactual reduction in the conditioned response or a reduction in the associability of the CS. This, it will be recalled, is similar to the problem encountered in a number of animal conditioning paradigms. In addition, these studies with humans may have included unplanned masking procedures – either by the very nature of the procedure or by instruction.

Let us now consider the effects of age and masking on latent inhibition in humans.

It is difficult to determine exactly when I began this book, as such. However, the research on latent inhibition was initiated in the late 1950s while I was still a graduate student at Cornell University. The next memorable date for measurement was the publication of an article reviewing the latent inhibition literature in the Psychological Bulletin (1973), which appeared in about half of its original length. The conditioned attention theory of latent inhibition was developed later in a series of articles in the Journal of Experimental Psychology: Animal Behavior Processes in the mid-1970s, and then presented more fully in a chapter in Progress in Learning and Motivation edited by G.H. Bower (1981). The idea of developing this material into a book emerged during a sabbatical year at Yale University, 1977–1978, while much of the writing itself was postponed until another sabbatical, 1981–1982, as an Israel-Canada Fellow at Concordia Unversity. To all of these institutions, and to the individuals who were responsible for inviting me, I express my sincerest gratitude, particularly to Allan Wagner and Eugene Rothman.

In addition, throughout the years I have been fortunate to have my research supported by a number of organizations: The National Institutes of Health were particularly encouraging, especially at the early stages of my career with a Career Development Award. Other support has come from the Scottish Rite Schizophrenia Research Program and, in Israel, from the Charles Smith Psychobiology Fund, the Israel National Academy of Science, Israel Research Trustees Foundation (Ford), and Tel-Aviv Unversity.

Similarity of preexposed stimulus and test stimulus

Studies of the influence of stimulus preexposure on subsequent learning usually assume that these effects are stimulus-specific. That is, preexposure to stimulus A should not retard the subsequent acquisition of an association between stimulus B and another event. This assumption is particularly critical if one maintains the idea that the subsequent decrement in the acquisition of the association between A and another event is a result of some previous associative learning during the preexposure phase. Associative learning, by definition, presumes some degree of stimulus specificity. Indeed, the apparent absence of such specificity in the learned helplessness effect, at least in rats (Maier & Seligman, 1976) in which preexposures of a motivationally significant stimulus is administered, by itself, might raise the question whether or not one is dealing with an associative learning phenomenon. For latent inhibition, across different paradigms, the results are quite clear. The decremental effects of preexposure of the to-be-conditioned stimulus on subsequent acquisition of a new association are, without doubt, stimulus-specific.

Such stimulus specificity may be demonstrated in several ways. (1) A within-subject experimental design may be employed whereby the animal is preexposed to stimulus A and tested on both stimulus A and stimulus B. When appropriately counterbalanced, slower learning to the familiar stimulus compared with the novel stimulus serves as evidence for the stimulus specificity of latent inhibition. Such a design was employed by Lubow and Moore (1959), Reiss and Wagner (1972), and Wickens et al. (1983).

Human behaviour is a key to health, and changes in behaviour have a profound influence on patterns of morbidity, and mortality from disease.

This fact is not a new discovery. From the earliest days of human history, behaviour has been the focus of most of the action aiming to prevent and treat illness. Dietary and hygienic prescriptions are embedded in most religions and rituals of mourning are undertaken by the bereaved to help them overcome stress. Societal relations are regulated to strengthen supportive social networks. In the past, links between behavioural change and the course of disease were frequently not well understood, and behavioural action was recommended because of the correlations observed – recommended nevertheless with force and insistence.

The twentieth century brought with it clear evidence of causal links between specific forms of behaviour – including attitudes, action and comprehension – and improvement or deterioration of health states. An impressive amount of literature has been produced over the past decades in this area, and both the public and the scientific community have become acutely aware of the need to influence behaviour if progress is to be made in promoting health, preventing disease, or decreasing suffering of those in whom it has appeared. Insistence that appropriate action be taken has not only stemmed from scientists; government leaders have also addressed the question. The World Health Assembly, bringing together chief health executives from 160 member states, for example, has devoted much of its time to the discussion of this matter.