Conditioned catalepsy vs. Increase in locomotor activity induced by haloperidol.

Previous research has revealed a high degree of complexity of the conditioned response that appears after associating a context with the effects of the dopaminergic antagonist haloperidol. Specifically, when a drug-free test is performed in the presence of the context, conditioned catalepsy is observed. However, if the test is extended over time, the opposite effect occurs, namely, a conditioned increase in locomotor activity. In this paper, we present the results of an experiment with rats that received repeated administration of haloperidol or saline before or after exposure to the context. Next, a drug-free test was performed to evaluate catalepsy and spontaneous locomotor activity. The results revealed, on the one hand, the expected conditioned response of catalepsy for those animals that received the drug prior to context exposure during conditioning. However, for the same group, an analysis of locomotor activity for an extended period of ten minutes after registering catalepsy revealed an increase in general activity and more faster movements compared to the control groups. These results are interpreted considering the possible temporal dynamics of the conditioned response that could induce changes in dopaminergic transmission responsible for the observed changes in locomotor activity.

Contextual control of flavor neophobia.

The role of context in the retrieval of learned information has been widely analyzed in the associative learning domain. However, evidence about the effect of context on flavor memory retrieval is more limited. We have carried out four experiments with rats testing for possible interactions between neophobia habituation and the context in which flavors are presented, by manipulating prior experience with contexts. Our results point to the relevance of context familiarity for the establishment and recovery of a safe taste memory trace. More specifically, the use of the animals' home cages as experimental context favored neophobia habituation (Experiments 1A and 2), reduced dopamine levels induced by administration of the dopamine D1-like receptor antagonist SCH-23390 disrupted neophobia habituation when tested in presence of a new context (Experiment 1B), and testing in the animal's home cage increases the amount of flavor consumed, even when such flavor had a previous history of aversive conditioning (Experiment 3). We propose that exploring context without aversive consequences generates a safe memory trace of such context that becomes in the basis of increased flavor consumption.

Different effects of unexpected changes in environmental conditions on prepulse inhibition in rats and humans.

The reduction of the startle response to an auditory stimulus caused by the presentation of another stimulus of lower intensity closely preceding it, a phenomenon known as prepulse inhibition (PPI), can be modulated by changes in dopaminergic activity. Schmajuk, Larrauri, De la Casa, and Levin (2009) demonstrated that this dopaminergic modulation of PPI in rats can be influenced by manipulating the experimental context, specifically by introducing changes in the ambient lighting condition that include novel elements. In this paper we analyze the effects of introducing changes in context illumination on PPI in male rats (Experiment 1) and humans (Experiment 2). The results with rats showed a reduction of PPI when the illumination condition switched from dark to light, but not from light to dark. In the experiment with human participants the reduction of PPI occurred for both changes in illumination conditions. The animal experiment results are interpreted in terms of competing exploratory behavior that appear when the context is illuminated after the dark-light transition; while in the case of human participants a perceptual and/or attentional mechanism after both illumination transitions is proposed, which may result in a reduced processing of the prepulse and subsequent lower PPI.

Effects of context novelty vs. familiarity on latent inhibition with a conditioned taste aversion procedure.

The latent inhibition phenomenon is observed when a conditioned stimulus is preexposed without any consequence before conditioning. The result of this manipulation is a reduction in conditioned response intensity to such a stimulus. In this study, we analyse the role of context novelty/familiarity on LI modulation by changing the context using a three-stage conditioned taste aversion procedure. Experiment 1 revealed that, similar to other learning procedures, a context change between preexposure and conditioning/testing (but not between preexposure/conditioning and testing) resulted in LI attenuation when the experimental contexts were novel. Experiment 2, using animals' home cages as one of the contexts, revealed a different pattern of results, with an unexpected increase in LI magnitude when the context change was introduced between conditioning and test stages. The Schmajuk et al. (1996) computational model explains these results in terms of the increased novelty of the conditioned stimulus during preexposure, conditioning, and testing.

Attenuation of auditory startle and prepulse inhibition by unexpected changes in ambient illumination through dopaminergic mechanisms.

We investigated the role of dopaminergic mechanisms in the attenuation of the acoustic startle response and prepulse inhibition (PPI) in rats by the introduction of unexpected changes in environment illumination. Experiment 1 showed that Dark-to-Light transitions robustly reduce startle responses and PPI. Experiment 2 showed that this phenomenon habituates across repeated testing sessions and reappears after an interval without testing. Experiment 3 demonstrated that haloperidol blocks the startle and PPI-reducing effect of the Dark-to-Light transition. We show how a computational model of acoustic startle response and prepulse inhibition can be extended to incorporate the empirical effects demonstrated in this study. We conclude that sensory gating as measured by prepulse inhibition is markedly attenuated in situations where novel stimuli are introduced during a test session and that dopaminergic systems may be involved in the dynamic changes evoked by the onset of illumination.

Ketamine blocks the formation of a gustatory memory trace in rats.

N-methyl-D-aspartate (NMDA) receptors appear to play a central role in learning and memory processes, as the administration of antagonistic substances of these receptors hinders learning acquisition by using different behavioral paradigms (e.g., Riedel G, Platt B, Micheau J. Glutamate receptor function in learning and memory. Behavioural Brain Research, 2003;140 (1-2):1-47.). In the specific case of conditioned taste aversion, the administration of ketamine seems to affect the acquisition of conditioning when the drugs are administered before the experimental treatment. In this paper we present three experiments designed to analyze the effect of different ketamine doses (25 mg/kg, 50 mg/kg, 75 mg/kg and 120 mg/kg), administered between exposure to a taste (the conditioned stimulus) and the administration of the unconditioned stimulus, on the acquisition of a taste aversion association. The results reveal that higher ketamine doses (75 mg/kg and 120 mg/kg) have a disruptive effect on conditioned taste aversion by impeding the formation of the gustatory trace.

Effects of preexposure and retention interval placement on latent inhibition and perceptual learning in a choice-maze discrimination task.

In two experiments, we examined how preexposure to discriminative stimuli and introduction of a 21-day retention interval affected the latent inhibition (LI) and perceptual learning (PL) of rats in a choice-maze discrimination task. Experimental groups were preexposed to three wall patterns, one in each of three arms of a maze. Control groups werepreexposed only towhite arms. PL groupswere trained to discriminate A versus B, and LI groups, to discriminate A or B versus C. The A and B patterns shared many elements not shared with the C pattern. In Experiment 1, both at the end of training and after the subsequent retention interval, the PL groups performed better than controls, whereas the LI groups performed worse. In Experiment 2, inserting the 21-day retention interval between preexposure and discrimination training disrupted final measures of LI but not PL performance. Implications for current concepts of PL and LI are discussed.

Delay-induced super-latent inhibition as a function of order of exposure to two flavours prior to compound conditioning.

A number of recent conditioned taste aversion (CTA) experiments have demonstrated a super-latent inhibition (LI) effect--namely, a time-induced increase in the effects of stimulus preexposure when the interval between acquisition and test is spent in a context that is different from the other experimental contexts. Two CTA experiments with rats were conducted to examine the role of primacy in producing super-LI. In Experiment 1, one of two flavours was pre-exposed, following which a second flavour was preexposed. After the second preexposure, animals were conditioned by pairing a compound of the two preexposed flavours with LiCl. The test stage was conducted 1 or 21 days after conditioning, with the interval being spent in either the same or different contexts. In the test, animals were confronted with two bottles, each with one of the two preexposed flavours. Super-LI was obtained only for the first preexposed flavour in the 21-day delay group that spent the interval in a different context. Experiment 2 was designed to ensure that the effects in Experiment 1 represented LI, and to control for order of presentation of the flavours and time between preexposure and acquisition. The results replicated those of Experiment 1. The two experiments support the importance of primacy in the general super-LI experiment where CS-alone preexposure precedes CS-US.

There is a time and a place for everything: bidirectional modulations of latent inhibition by time-induced context differentiation.

Latent inhibition (LI) is defined as poorer evidence of learning with a stimulus that previously was presented without consequence, as compared with a novel or previously attended stimulus. The present article reviews the evidence, mostly from three-stage conditioned taste aversion studies (preexposure, conditioning, and test), that LI can be either attenuated or enhanced depending on the length of the retention interval between conditioning and test and where that interval was spent. Time-induced reduction in LI is observed when the interval context is the same as that of the preexposure, conditioning, and test stages. Super-LI is obtained when a long retention interval is spent in a context that is different from that of the other stages. The differential modulations of LI appear to be the result of the strengthening of primacy effects (i.e., first training disproportionately stronger than subsequent training) by long-interval different contexts, thereby producing super-LI, and the reversal of this effect by long-interval same contexts, thereby producing attenuated LI. The bidirectional effects of time/ context modulations on LI, unaccounted for by current learning theories, are explained, in part, by a time-induced context differentiation process. Implications for theories of LI, learning, and, memory are discussed.

Latent inhibition disruption by MK-801 in a conditioned taste-aversion paradigm.

N-Methyl-D-aspartate (NMDA) receptors appear to be involved in CS processing and memory consolidation. The present paper analyzed the effect of the non-competitive NMDA receptor antagonist Dizocilpine maleate (MK-801) on Latent Inhibition (LI)-retarded learning of a CS-US association after to-be-CS preexposures at time of testing, using Wistar rats as experimental subjects. If NMDA receptors are involved in CS processing, MK-801 administration should affect LI. In fact, previous experiments revealed that a 2.0mg/kg MK-801 dose, administered 20 h before preexposure and conditioning, abolished LI in a conditioned taste-aversion paradigm. In the present paper, MK-801 (0.2 mg/kg) was either injected after preexposure, after conditioning, or after both preexposure and conditioning stages. LI was abolished when MK-801 was injected after preexposure, but not when it was injected after conditioning. These results support the role of NMDA receptors in CS processing and memory consolidation.

Effects of post-treatment retention interval and context on neophobia and conditioned taste aversion.

We have repeatedly observed that a delay between acquisition and test, and the nature of the context in which the delay is spent, modulates latent inhibition (LI) of conditioned taste aversion (CTA; e.g. [Anim. Learn. Behav. 28 (2000) 389; Anim. Learn. Behav. 30 (2002) 112]). The present paper analysed the effects of delayed testing and treatment context after flavor exposure on the recovery of neophobia (Experiment 1) and on extinction after simple conditioning (Experiment 2). Two experiments were conducted with the same factorial design (2x2: 1 day versus 21 days of delay between first and second stage, and home versus experimental cages as place of experimental treatment). There were independent effects of both variables on habituation of neophobia and conditioning strength as measured on extinction trials. The long delay produced a reduction of neophobia (Experiment 1) and an increase in conditioning (Experiment 2). In addition, more of the flavored solution was consumed when the experimental treatment was conducted in the home cage than in the experimental cage (Experiment 1), and there was stronger conditioning when the delay period took place in the experimental cages than in the home cages (Experiment 2). The implications of these results for LI, as well as their relevance for experiments that use the CTA paradigm, are discussed.

An empirical analysis of the super-latent inhibition effect.

In three conditioned taste aversion experiments, we examined the roles of several variables in producing super-latent inhibition (LI). This effect, greater LI after a long interval than after a short interval between the conditioning and the test stages (De la Casa & Lubow, 2000), was shown to increase with the number of stimulus preexposures (0, 2, or 4; Experiment 1) and with the length of the delay interval (1, 7, 14, or 21 days; Experiment 2). Furthermore, super-LI was obtained when the delay interval was introduced between the conditioning and the test stages (Experiments 1 and 2), but not when it was introduced between the preexposure and the conditioning stages (Experiment 3). The results are discussed in relation to interference explanations of LI.

Superlatent inhibition and spontaneous recovery: differential effects of pre- and postconditioning CS-alone presentations after long delays in different contexts.

In two pairs of three-stage conditioned taste aversion experiments, we examined the effects of delay interval (1 or 21 days) between the second and third stages, and of context in which the animals spent the delay (same as or different from the context of the other stages) on latent inhibition (LI) and spontaneous recovery following extinction. In the LI experiments (Experiments 1A and 1B), the first stage comprised nonreinforced presentations to saccharin or to water. In the second stage, rats were conditioned by saccharin paired with LiCl. In the extinction experiments (Experiments 2A and 2B), the order of the stages was reversed. For all experiments, Stage 3, the test stage, consisted of three presentations of saccharin alone. There was a super-LI effect in the saccharin-preexposed group that spent the 21-day delay in the different context (Experiment 1A). When the delay was spent in the same context, there was no difference in the amount of LI between the short- and long-delay groups (Experiment 1B). Conversely, there was a spontaneous recovery effect in the long-delay/same-context group (Experiment 2B), but not in the long-delay/different-context group (Experiment 2A). The pattern of results, incompatible with current explanations of delay-induced changes in memory performance, was interpreted in terms of an interaction between the delay conditions (same or different delay context), which modulate the extinction of previously acquired context-CS-nothing associations (during CS-alone presentations), and primacy effects.

Latent inhibition with a response time measure from a within-subject design: effects of number of preexposures, masking task, context change, and delay.

Latent inhibition (LI), poorer performance on a learning task to a previously irrelevant stimulus than to a novel stimulus, was produced in 4 experiments, using a within-subject design and a response time (RT) measure. LI was reduced by decreasing the number of stimulus preexposures, omitting the masking task, changing the context from the preexposure to the test phase, and introducing a delay between the 2 phases. Together, these effects indicate that the within-subject RT-based LI reflects the same processes as those that govern between-subject LI with correct response as the dependent measure. The new procedure provides an advantageous method for assessing attentional dysfunction related to the processing of irrelevant stimuli, particularly in pathological groups, such as patients with schizophrenia.

Amphetamine-produced attenuation of latent inhibition is modulated by stimulus preexposure duration: implications for schizophrenia.

The relationship between amphetamine-produced dopamine overreactivity and attention to irrelevant stimuli is reflected in an attenuated latent inhibition (LI) effect. This occurs in both animal and human subjects. The present study examines the manner in which this effect in rats is modulated by the duration of stimulus preexposure. A factorial design was used with three levels of stimulus preexposure duration and either amphetamine or saline administration. In addition, there were corresponding groups that did not receive stimulus preexposure. It was found that although amphetamine did indeed abolish LI at short exposure intervals (30 sec), the LI effect was normal for long stimulus preexposure durations (150 sec). The data were discussed in terms of the affects of amphetamine on the processing of irrelevant stimuli and the relationship of such a dysfunctional attentional process to schizophrenia.

Latent inhibition and recall/recognition of irrelevant stimuli as a function of pre-exposure duration in high and low psychotic-prone normal subjects.

Learning to ignore non-relevant stimuli (coloured geometric shapes) was evaluated in high and low psychotic-prone normal subjects in two experiments. In the first, subjects were tested in a latent inhibition paradigm in a 2 x 2 x 3 factorial design (high vs. low psychotic proneness, as measured by MMPI subscales; pre-exposure of the stimuli such that they were non-relevant before the test but relevant in the test vs. absence of such pre-exposure; three levels of pre-exposure duration: 3-, 6- and 15-min). Low psychotic-prone subjects showed the latent inhibition effect (poorer learning as a result of pre-exposure to the non-relevant stimuli as compared to no pre-exposure) at 6- and 15-min durations, but not at 3-min. High psychotic-prone subjects failed to show latent inhibition at 3- and 6-min durations, but did show the effect at 15-min. The second experiment employed a 2 x 3 design (high vs. low psychotic proneness; three levels of pre-exposure duration of the same stimuli used in Expt 1). High psychotic-prone normal subjects recalled and recognized more previously non-relevant stimuli than low psychotic-prone subjects, particularly after 6-min pre-exposure to those stimuli. The data of the two experiments suggest that the attenuation of latent inhibition in high psychotic-prone subjects as compared to low psychotic-prone subjects is a result of the increased attention to non-relevant information.