Luis Gonzalo De la Casa

Taste memory trace disruption by AP5 administration in basolateral amygdala

N-methyl-D-aspartate receptor has been related to learning and memory processes. Its characteristics make it a key candidate in the modulation of associative processes at physiological level. Traditionally, the main efforts have been directed to show its role in excitatory conditioning. Nevertheless, the studies that have analyzed its implication in inhibitory learning are scarce. We present an experiment where a preexposure effect on the conditioning (latent inhibition) is disrupted by 2-amino-5-phosphonopentanoic acid administered in basolateral amygdala. This data shows interference on taste memory trace, and attenuation of the inhibition effect.

Reduced Prepulse Inhibition as a Biomarker of Schizophrenia

The startle response is composed by a set of reflex behaviors intended to prepare the organism to face a potentially relevant stimulus. This response can be modulated by several factors as, for example, repeated presentations of the stimulus (startle habituation), or by previous presentation of a weak stimulus (Prepulse Inhibition [PPI]). Both phenomena appear disrupted in schizophrenia that is thought to reflect an alteration in dopaminergic and glutamatergic neurotransmission. In this paper we analyze whether the reported deficits are indicating a transient effect restricted to the acute phase of the disease, or if it reflects a more general biomarker or endophenotype of the disorder. To this end, we measured startle responses in the same set of thirteen schizophrenia patients with a cross-sectional design at two periods: 5 days after hospital admission and 3 months after discharge. The results showed that both startle habituation and PPI were impaired in the schizophrenia patients at the acute stage as compared to a control group composed by 13 healthy participants, and that PPI but not startle habituation remained disrupted when registered 3 months after the discharge. These data point to the consideration of PPI, but not startle habituation, as a schizophrenia biomarker.

Differential implication of dorsolateral and dorsomedial srtiatum in encoding and recovery processes of latent inhibition.

The dorsal striatum has been ascribed to different behavioral roles. While the lateral area (dls) is implicated in habitual actions, its medial part (dms) is linked to goal expectancy. According to this model, dls function includes representation of stimulus-response associations, but not of goals. Dls function has been typically analyzed with regard to movement, and there is no data indicating whether this region could processes specific stimulus-outcome associations. To test this possibility, we analyzed the effects of dls and dms inactivation on the retrieval phase, and dms lesion on the acquisition phase of a latent inhibition procedure using two conditions, long and short presentations of the future conditioned stimulus. Contrary to current theories of basal ganglia function, we report evidence in favor of the dls involvement in cognitive processes of learning and retrieval. Moreover, we provide data about the sequential relationship between dms and dls, in which the dms could be involved, but it would not be critical, in new learning and the dls could be subsequently involved in consolidating cognitive routines.

MK-801 induces a low intensity conditioned taste aversion.

N-methyl-D-aspartate (NMDA) receptor antagonists are often used to assess the role of NMDA receptors in learning and memory processes. However, few studies have explored the possibility that the antagonists may induce a conditioned aversion when administered following flavor consumption. We report five experiments with rats intended to evaluate the MK-801 capacity to induce conditioned taste aversion. Our findings suggest that: i) MK-801 produces a low-intensity aversion following repeated pairings with saccharin (Experiments 1 and 2); ii) such aversion was not the result of a non-associative process (Experiment 3); and iii) pre-exposure to MK-801 does not interact with conditioned taste aversion induced by lithium chloride (Experiments 4 and 5). These findings suggest that MK-801 induces a low-intensity aversion, although the underlying mechanisms of this aversion may differ from those of a conditioned aversion produced by lithium chloride.

Pavlov in America: A Heterodox Approach to the Study of his Influence

This work presents a critical analysis of Pavlovs influence that goes beyond the conventional view: that which reduces his influence in American psychology to the behaviorism of Watson and Hull. In order to understand the nature of the Russian physiologists influence in American psychology, we propose a distinction between three approaches to it: 1) the symbolic approach, on representing a model of the possibility of constructing an objective psychology; 2) the methodological approach, given the importance of the technique of conditional reflexes; and 3) the theoretical approach, which is derived from his theory of higher nervous activity. This perspective permits us to suggest that most of Pavlovs influence on behaviorism was of a symbolic and methodological nature--though the methodological influence also reached other authors that did not belong to the behaviorist traditions, as was the case of Mateer. As far as the theoretical influence is concerned, our work proposes that it is more visible in authors such as Gantt and Liddell, or even in authors such as Boldirev, Director of the Pavlovian Laboratory at the Battle Creek Sanitarium in Michigan. The case of Gantt is especially interesting because, in addition to his important contributions, he played an essential role in the foundation of the Pavlovian Society, and the journal Conditional Reflex. What our work proposes is that to understand the nature of Pavlovs influence in American psychology it is necessary to take into account the very characteristics of that psychology: its pragmatic interests, its methodological rigor, the dominant systems of neo-behavioral theory and the changes that occurred after the Second World War.

Effect of stress and attention on startle response and prepulse inhibition

The startle reflex magnitude can be modulated when a weak stimulus is presented before the onset of the startle stimulus, a phenomenon termed prepulse inhibition (PPI). Previous research has demonstrated that emotional processes can modulate PPI and startle intensity, but the available evidence is inconclusive. In order to obtain additional evidence in this domain, we conducted two experiments intended to analyze the effect of induced stress and attentional load on PPI and startle magnitude. Specifically, in Experiment 1 we used a between subject strategy to evaluate the effect on startle response and PPI magnitude of performing a difficult task intended to induce stress in the participants, as compared to a group exposed to a control task. In Experiment 2 we evaluated the effect of diverting attention from the acoustic stimulus on startle and PPI intensity. The results seem to indicate that induced stress can reduce PPI, and that startle reflex intensity is reduced when attention is directed away from the auditory stimulus that induces the reflex.

Food and water deprivation disrupts latent inhibition with an auditory fear conditioning procedure.

Latent inhibition (LI), operationally defined as the reduced conditioned response to a stimulus that has been preexposed before conditioning, seems to be determined by the interaction of different processes that includes attentional, associative, memory, motivational, and emotional factors. In this paper we focused on the role of deprivation level on LI intensity using an auditory fear conditioning procedure with rats. LI was observed when the animals were non-deprived, but it was disrupted when the rats were water- or food-deprived. We propose that deprivation induced an increase in attention to the to-be-CS, and, as a result, LI was disrupted in deprived animals. The implications of the results for the current interpretations of LI are also discussed.Latent inhibition (LI), operationally defined as the reduced conditioned response to a stimulus that has been preexposed before conditioning, seems to be determined by the interaction of different processes that includes attentional, associative, memory, motivational, and emotional factors. In this paper we focused on the role of deprivation level on LI intensity using an auditory fear conditioning procedure with rats. LI was observed when the animals were non-deprived, but it was disrupted when the rats were water- or food-deprived. We propose that deprivation induced an increase in attention to the to-be-CS, and, as a result, LI was disrupted in deprived animals. The implications of the results for the current interpretations of LI are also discussed.

Effect of the NMDA antagonist MK-801 on latent inhibition of fear conditioning

N-methyl-D-aspartate (NMDA) receptors seem to play a central role in learning and memory processes involved in Latent Inhibition (LI). In fact, MK-801, a non-competitive NMDA receptor antagonist, has proved its effectiveness as a drug for attenuating LI when administered before or after stimulus preexposure and conditioning stages. This paper presents three experiments designed to analyze the effect of MK-801 on LI when the drug is administered before (Experiment 1A) or after (Experiment 1B) preexposure and conditioning stages with a conditioned emotional response procedure. Additionally, we analyze the effect of the drug when it was administered before preexposure, before conditioning or before both phases (Experiment 2). The results show that the effect of the drug varied as a function of the dose (with only the highest dose being effective), the moment of administration (with only the drug administered before the experimental treatments being effective), and the phase of procedure (reducing LI when the drug was administered only at preexposure, and disrupting fear conditioning when administered at conditioning). These differences may be due to several factors ranging from the role played by NMDA receptors in the processing of stimuli of different sensorial modalities to the molecular processes triggered by drug administration.

Prepulse inhibition modulation by contextual conditioning of dopaminergic activity

When a neutral stimulus is repeatedly paired with a drug, an association is established between them that can induce two different responses: either an opponent response that counteracts the effect of the drug, or a response that is similar to that induced by the drug. In this paper, we focus on the analysis of the associations that can be established between the contextual cues and the administration of dopamine agonists or antagonists. Our hypothesis suggests that repeated administration of drugs that modulate dopaminergic activity in the presence of a specific context leads to the establishment of an association that subsequently results in a conditioned response to the context that is similar to that induced by the drug. To test this hypothesis, we conducted two experiments that revealed that contextual cues acquired the property to modulate pre-pulse inhibition by prior pairings of such context with the dopamine antagonist haloperidol (Experiment 1), and with the dopamine agonist d-amphetamine (Experiment 2). The implications of these results are discussed both at a theoretical level, and attending to the possibilities that could involve the use of context cues for the therapeutic administration of dopaminergic drugs.

Conditioned increase of locomotor activity induced by haloperidol

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol can act as an unconditioned stimulus, we carried out two experiments in which the administration of haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase in locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.