Latent inhibition is affected by phase of estrous cycle in female rats

Estrogen has been shown to have a strong modulatory influence on several types of cognition in both women and female rodents. Latent inhibition is a task in which pre-exposure to a neutral stimulus, such as a tone, later impedes the association of that stimulus with a particular consequence, such as a shock. Previous work from our lab demonstrates that high levels of estradiol (E2) administered to ovariectomized (OVX) female rats abolishes latent inhibition when compared to female rats with low levels of E2 or male rats. To determine if this E2-induced impairment also occurs with the natural variations of ovarian hormones during the estrous cycle, this behavior was investigated in cycling female rats. In addition, pre-pubertal male and female rats were also tested in this paradigm to determine if the previously described sex differences are activational or organizational in nature. In a latent inhibition paradigm using a tone and a shock, adult rats were conditioned during different points of the estrous cycle. Rats conditioned during proestrus, a period of high E2 levels, exhibited attenuated latent inhibition when compared to rats conditioned during estrus or metestrus, periods associated with low levels of E2. Moreover, this effect is not seen until puberty indicating it is dependent on the surge of hormones at puberty. This study confirms recent findings that high E2 interferes with latent inhibition and is the first to show this is based in the activational actions of hormones.     

Enhanced latent inhibition in context aversion conditioning

In four experiments, we investigated the effect of giving rats exposure to a distinctive environmental context before a phase of training in which an injection of LiCl was paired with that context. The results of Experiments 1 and 2 were consistent with the possibility that such preexposure served to retard subsequent conditioning to the context (i.e., produced a latent inhibition effect). Experiments 3 and 4 demonstrated that allowing the rats to consume a novel-flavored solution during preexposure enhanced the latent inhibition effect. The relevance of these findings both for theories of latent inhibition and for the use of preexposure as a clinical intervention for the reduction of conditioned nausea in humans is considered.     

Some determinants of latent inhibition in human predictive learning

The present experiments assessed the effects of different manipulations between cue preexposure and cue-outcome pairings on latent inhibition (LI) in a predictive learning task with human participants. To facilitate LI, preexposure and acquisition with the target cues took place while participants performed a secondary task. Presentation of neither the target cues nor the target outcome was anticipated based on the instructions. Experiment 1 demonstrated the LI effect in the new experimental preparation. Experiment 2 analyzed the impact on LI of different activities that participants performed during the interval between preexposure and acquisition. Experiment 3 assessed LI as a function of changes in the secondary task cues made between preexposure and acquisition, namely presenting novel cues and reversing the cue-outcome contingencies. All of the manipulations in Experiments 2 and 3 resulted in a decrease in LI. The attenuation of LI by these manipulations challenges most current theories of learning and is best accommodated by Conditioned Attention Theory (Lubow, Weiner, & Schnur, 1981).     

Differences in latent inhibition as a function of the autogenous-reactive OCD subtype

We examined differences in a visual search-based latent inhibition (LI) task in 48 non-treatment seeking individuals diagnosed with obsessive-compulsive disorder (OCD) and 26 non-OCD controls, using a visual search-based LI task as a function of participants’ primary obsessional presentation based on the autogenous-reactive subtype model of obsessions ( [Lee and Telch, 2005] and [Lee and Telch, 2007]). We hypothesized that LI would be significantly attenuated among OCD participants whose primary obsessions were characterized by aversive impulses, images, or thoughts with sexual, aggressive, blasphemous, and repulsive themes (autogenous obsessions) due to their weakened attentional inhibitory mechanisms and elevated schizotypal personality features, as compared with those whose primary obsessions were characterized by somewhat realistic aversive mental intrusions about contamination, mistakes, accidents, or disarray (reactive obsession) and non-OCD controls. Results showed that those primarily displaying autogenous obsessions failed to display LI, whereas those primarily displaying reactive obsessions and non-OCD controls displayed significant LI effects. Our data suggest that the magnitude of LI varies as a function of primary obsessional presentations among individuals with OCD.     

Further evidence for the summation of latent inhibition and overshadowing in rats’ conditioned taste aversion

Repeated exposures to a target taste (X) attenuated subsequent development of rats’ conditioned aversion to X (latent inhibition effect). Presentation of another taste (A) after X in conditioning (serial X-A compound conditioning) also attenuated conditioned X aversion compared with conditioning without A (overshadowing). Furthermore, the latent inhibition and overshadowing effects summed to show the least conditioned aversion in the rats given both the target preexposures and the serial X-A compound conditioning treatment. These results question the validity of the comparator hypothesis as an explanation for Pavlovian conditioning of rats’ conditioned taste aversion.     

Human latent inhibition and the density of predictive relationships in the context in which the target stimulus occurs

In two experiments, participants were exposed to a listing of actions performed by a fictitious Mr. X, over three days of his life. For most of his actions an outcome was described, but some were not followed by any outcome. On Day 3, Mr. X performed an action (the target action) that was followed by a novel outcome. For participants in the control condition, the target action that preceded the appearance of this outcome was also novel; for participants in the latent inhibition (LI) condition, Mr. X had performed the target action on repeated occasions during Days 2 and 3, without it producing any outcome. All the participants were tested on their ability to retrieve the action performed by Mr. X prior to the target outcome. In Experiment 1, retrieval of the target action (indicating a less effective target action–outcome association) was poorer in the LI than in the control condition. In Experiment 2, reducing the proportion (the density) of nontarget actions that brought outcomes during initial training was found to reduce the size of the LI effect. These results are predicted by the account of LI put forward previously [Hall, G., & Rodríguez, G. (2010). Associative and nonassociative processes in latent inhibition: An elaboration of the Pearce-Hall model. In R. E. Lubow & I. Weiner (Eds.), Latent inhibition: Data, theories, and applications to schizophrenia (pp. 114–136). Cambridge, England: Cambridge University Press]. A high density of predictive relationships ensures strong activation of the expectancy that some outcome will occur when the target action is first presented; this facilitates the formation of a target action–no-event association during training in the LI condition, thus enhancing the LI effect.     

Overshadowing and latent inhibition in nausea-based context conditioning in humans: Theoretical and practical implications

Volunteer participants underwent nausea-inducing body rotation in a distinctive context, and the acquired ability of the contextual cues to evoke nausea was subsequently assessed by a symptom rating scale. One group received prior exposure to the context (a latent inhibition procedure); a second consumed a novel flavour prior to rotation (an overshadowing procedure); a third group experienced both procedures; and a control group received neither. When tested in the context in the absence of rotation, all groups reported an increase in nausea-related symptoms at the time when rotation had previously occurred, an outcome consistent with the occurrence of conditioned nausea. The magnitude of this increase did not differ across the groups, but the overall level of responsiveness (the degree to which nausea-related symptoms were reported) was enhanced in the latent inhibition and reduced in the overshadowing condition. Cortisol levels showed the same pattern. The implications of these findings for the proposal that overshadowing and latent inhibition procedures might be used to control the development of anticipatory nausea in patients undergoing chemotherapy is considered.     

The interaction between schizotypy and latent inhibition: modulation by experimental parameters

Two recent experiments (Della Casa et al., in press) yielded the typical reduced latent inhibition (LI) in high vs low schizotypy subjects after a slow, irregularly presented masking task (Stroop task), and reduced LI in low vs high schizotypy subjects after a fast, regularly presented masking task. The present experiment was aimed at testing whether speed or regularity was responsible for the different results. The present slow, regular experiment replicated the results of the former slow, irregular experiment, i.e. reduced LI in high schizotypals and significant LI in low schizotypals, indicating that speed and not regularity is the critical experimental variable. The modulation of the schizotypy—latent inhibition relationship can be attributed to differences in attentional resources or the time available to process the to-be-target stimuli during preexposure, in accordance with the hypothesis of Lubow and Gewirtz, 1995 that automatic processing of these stimuli is critical for the development of latent inhibition in adult humans. In addition, results on Stroop and negative priming effects are presented.     

Obsessive-compulsive disorder patients display enhanced latent inhibition on a visual search task

Latent inhibition (LI) is a phenomenon that reflects the ability to ignore irrelevant stimuli. LI is attenuated in some schizophrenic patient groups and in high schizotypal normal participants. One study has found enhanced LI in patients with obsessive-compulsive disorder (OCD [Swerdlow, N. R., Hartston, H. J., & Hartman, P. L., 1999. Enhanced visual latent inhibition in obsessive-compulsive disorder. Biological Psychiatry, 45, 482-488]). The present experiment replicated this finding using a within-subject visual search LI task, with OCD patients displaying more LI than healthy controls. The contrasting LI effects in schizophrenia and OCD are discussed in terms of how these groups differentially process relevant and irrelevant stimuli, and how that outcome affects subsequent behavior.     

Higher levels of estradiol replacement correlate with better spatial memory in surgically menopausal young and middle-aged rats

The current study investigated whether, for spatial reference memory, age impacts (1) sensitivity to surgical ovarian hormone loss (Ovx), (2) response to estradiol therapy (ET), and (3) the relation between circulating estradiol levels and memory scores in ovary-intact sham and Ovx plus ET rats. Young, middle-aged and aged Fischer-344 rats received sham, Ovx or Ovx plus ET treatments, and were then tested on the Morris maze. After the last test trial, a probe trial was given whereby the platform was removed. Circulating estradiol levels were then determined and correlated with performance. In Study 1, Ovx facilitated learning on day one, but impaired performance after day one, in young rats. Ovx did not influence performance in middle-aged rats. In young and middle-aged Ovx rats, ET enhanced performance with higher exogenous estradiol levels correlating with better performance during testing and the probe trial. There was no relationship between endogenous estradiol levels and performance in sham young or middle-aged rats. Study 2 showed that, like middle-aged rats, aged rats were not impacted by Ovx. Further, for aged Ovx rats, the ET regimen that was beneficial at earlier ages was no longer effective during test trials, and had only minor benefits for platform localization as assessed by the probe trial. Collectively, the findings suggest that the effects of Ovx as well as responsivity to the currently utilized ET regimen changes with age. Further, there appears to be a distinction between sensitivity to Ovx and responsiveness to ET after Ovx for spatial reference memory performance.     

Distractor effect on the latent inhibition of conditioned flavor aversion in rats

Using a conditioned flavor aversion procedure with rats as subjects, the effect of the addition of a distractor stimulus on the magnitude of the latent inhibition effect was examined. Experiment 1 showed that latent inhibition to vinegar was attenuated by the addition of sucrose during preexposure. On the other hand, sucrose added during conditioning to vinegar did not attenuate latent inhibition. It was also found that the degree of latent inhibition to the vinegar-sucrose compound solution was less when vinegar alone was preexposed (i.e., when sucrose was added only during conditioning) than when the compound solution was preexposed (i.e., when sucrose was added both during preexposure and during conditioning). Experiment 2 gave similar results but with sucrose assigned as the target flavor and vinegar as the distractor. These findings are in full agreement with the generalization decrement account of latent inhibition.     

Attenuation of latent inhibition after compound conditioning

Using a conditioned suppression procedure with rats, three experiments examined the effects of compound conditioning on the degree of latent inhibition. Experiment 1 suggested that latent inhibition of the preexposed target was not enhanced but rather attenuated when a second stimulus was presented in compound conditioning. Experiment 2 showed that a similar result was obtained when, in subjects given only compound conditioning, the salience of the target was reduced to the level where it was overshadowed by the second stimulus. Experiment 3 proved that addition of the second stimulus only during preexposure, or during both preexposure and conditioning, did not attenuate the latent inhibition to the target. These results are difficult to explain by any model of Pavlovian conditioning which assumes that both latent inhibition and overshadowing effects are a consequence of acquisition deà cit; other possible accounts are discussed.     

Short-term estrogen treatment in ovariectomized rats augments hippocampal acetylcholine release during place learning

Estrogen modulates learning and memory in ovariectomized and naturally cycling female rats, especially in tasks using spatial learning and navigation. Estrogen also modulates cholinergic function in various forebrain structures. Past studies have shown positive correlations between hippocampal ACh output and performance on hippocampus-dependent tasks. The present study examined whether estradiol replacement would potentiate hippocampal ACh release during place learning. In vivo microdialysis and HPLC were used to measure extracellular ACh levels in the hippocampus of ovariectomized female rats that had received s.c. injections of 17beta-estradiol (10 microg) or sesame oil (vehicle treatment) 48 and 24h prior to training on a place task. Estrogen did not alter baseline levels of extracellular ACh in the hippocampus. During training, hippocampal ACh increased in ovariectomized rats regardless of estrogen status. However, while estradiol did not enhance learning in this experiment, estradiol significantly potentiated the increase in hippocampal ACh release seen during place training. This represents the first demonstration of on-line assessment of ACh output in hippocampus during learning in female rats and suggests that estrogen-dependent modulation of ACh release during training might control activation of different neural systems used during learning.     

Estrogen replacement in ovariectomized rats affects strategy selection in the Morris water maze

While estrogen enhances performance on some tasks of learning and memory, it has impairing or no effects on others. It has been proposed that estrogen differentially affects performance on various tasks of learning and memory by influencing the strategy used to solve a task. The goal of the present study was to determine if estrogen would influence strategy selection in the Morris water maze. Long-Evans rats were ovariectomized and implanted with Silastic capsules containing 25% estradiol diluted in cholesterol or 100% cholesterol. Rats were trained in a water maze task in which multiple strategies were available for use to locate a hidden escape platform that was moved to a new location for each set of four daily trials. During 10 days of acquisition trials, a visible floating landmark was always located in a static position relative to the hidden escape platform. Additionally, fixed extramaze cues visible to the animals surrounded the maze. Following acquisition, 2 days of probe trials were conducted in which the static landmark was removed. Estrogen replacement in ovariectomized rats resulted in impaired performance across 10 days of acquisition. Additionally, while removal of the visible landmark during the probe trials had no effect on the performance of the females receiving estrogen, it significantly disrupted performance of females receiving cholesterol treatment. These results indicate that estrogen replacement in ovariectomized rats biases an animal against using a landmark or static cue to aid in the location of a hidden escape platform in the water maze.     

Latent inhibition in within-subject designs: The roles of masking, schizotypy, and gender

Latent inhibition (LI) is defined as poorer associative learning with a previously exposed, irrelevant stimulus than with a non-preexposed, novel stimulus. This study examined how type of within-subject procedure, class of schizotypal symptoms, and gender modulate LI. Two within-subject procedures were examined, one excluding, and one including a masking task. The former yielded a stronger stimulus preexposure effect than the latter. However, the stimulus preexposure effect was attenuated by total schizotypy score in the masked, but not in the non-masked procedure. The results with schizotypy factors (positive and negative symptoms) as well as with schizotypy factors × gender interactions were inconsistent with those of other studies. It was suggested that in addition to LI, interference and novel pop-out effects were also produced by the procedures, particularly in the non-masked condition.     

Time of day-dependent latent inhibition of conditioned taste aversions in rats

We have determined that the temporal context of drinking can modulate latent inhibition of learned saline aversions in Wistar rats by changing the time of day of drinking of the preexposure and conditioning phases. Latent inhibition was absent in the group preexposed and conditioned to saline at different times of the day, but not in the group that was preexposed and conditioned at the same time of day. The results confirm a previous report that the time of day can modulate taste aversion learning independently of other environmental cues. It is proposed that the features and duration of the habituation training to the temporal contexts used may be critical for time-dependent latent inhibition to appear.     

Latent inhibition and context change in psychometrically defined schizotypy

The disruption of latent inhibition within the schizophrenia spectrum has often been interpreted either as a result of increased attentional distractibility (attentional account) or as a result of deficient interference of past associations (associative account). The aim of the present investigation was to test competing predictions, as derived from the above theoretical accounts. In a visual search paradigm of latent inhibition, accuracy was examined as a function of prior experience with the target, and psychometrically defined schizotypy. In Experiment 1 (N=60), no context change was introduced. In accord with past evidence, latent inhibition was found to be intact in low-, but disrupted in high-schizotypy scorers, a result predicted both by attentional and associative accounts. In Experiment 2 (N=60), a context change was introduced. As predicted by past evidence, latent inhibition was disrupted in low-schizotypy scorers. However, latent inhibition was found to be intact in high-schizotypy scorers, a finding accommodated by attentional, but not associative accounts. Theoretical implications and alternative interpretations are also considered.     

The effects of preexposure-test and conditioning-test intervals on the magnitude of latent inhibition

Using the conditioned taste aversion paradigm, two experiments were conducted to examine the effects of the interval between preexposure and test and that between conditioning and test on the magnitude of latent inhibition. Experiment 1 revealed that the degree of latent inhibition was attenuated when rats were given a 21‐day interval between preexposure and test. It was also found that this attenuation was more marked in subjects which were given conditioning immediately after preexposure than those which were conditioned shortly before the test. Retention interval between preexposure and test was reduced to 12 days in Experiment 2, and exactly the same pattern of results as those found in Experiment 1 was obtained. These findings suggest that the memory of conditioning as well as that of preexposure decreases its retrievability after a long retention interval, although the former is more retainable than the latter.     

Illegitimate concept equating in the partial fusion of construct validation theory and latent variable modeling

There has come to exist a partial fusion of construct validation theory and latent variable modeling at the center of which is located a practice of equating concepts such as construct, factor, latent variable, concept, unobservable, unmeasurable, underlying, hypothetical variable, theoretical term, theoretical variable, intervening variable, cause, abstractive property, functional unity, and measured property. In the current paper we: a) provide a structural explanation of this concept equating; b) provide arguments to the effect that it is illegitimate; c) suggest that the singular reason for the presence of construct in the literature of the social and behavioral sciences is to mark an allowance taken by the social and behavioral scientist to obliterate the concept/referent distinction that is foundational of sound science.     

Hippocampal lesions attenuate latent inhibition and the decline of the orienting response in rats

Two experiments using rats assessed the effect of dorsal hippocampal lesions on the orienting response (OR) elicited by a discrete light and on the subsequent associability of that light. In both experiments subjects received extensive nonreinforced exposure to the light, and it was found that the decline in the OR evident in sham-operated animals was severely attenuated by hippocampal lesions. Subsequently the light was paired with condensed milk in Experiment 1, and it was found that conditioning was faster in the lesioned than in the sham-operated group. Experiment 2 used a conditioned inhibition procedure whereby the light was presented in a nonreinforced compound with a tone which, when presented alone, acted as a signal for condensed milk. Again this discrimination was mastered more rapidly by lesioned animals. Relevant control groups indicated no differences between lesioned and sham-operated animals in learning about a novel light. Thus, hippocampal lesions influence both the loss of associability of a stimulus and the decline in the OR it elicits, which, in turn, suggests that the OR acts as an index of stimulus associability.