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.

Psychological pain and opioid receptors: Reward downshift is disrupted when tested in a context signaling morphine.

A sucrose downshift causes a temporary suppression of consumption accompanied by psychological pain, a negative emotion triggered by reward loss. When administered systemically before downshift sessions, opioid agonists reduce and opioid antagonists enhance such behavioral suppression. However, little is known about the effects of signals of opioid drugs on behavior during a reward downshift episode. Research showed that morphine administration can induce a direct effect (e.g., hypoalgesia) followed by a compensatory effect (e.g., hyperalgesia). Therefore, a signal for morphine could elicit either a direct or a compensatory effect. Male Wistar rats were exposed to ten 5-min sessions of access to 32% sucrose in context A, followed by three sessions of access to 4% sucrose in context B. In parallel, animals received pairings between context B and morphine (5 mg/kg, sc) occurring each day immediately after sucrose sessions (contexts were counterbalanced). Control conditions included a saline control (no morphine injected), an unpaired control (morphine injected after exposure to B) tested in A (Experiment 1), and an unpaired control tested in B (Experiment 2). In both experiments, behavioral suppression induced by the 32-to-4% sucrose downshift was attenuated when the downshift occurred in a context previously paired with morphine. These data are consistent with the hypothesis that reward downshift is accompanied by an emotion of negative valence that can be counteracted by the conditioned release of endogenous opioids triggered by signals of morphine, much like it is attenuated by systemic morphine administration. Alternative hypotheses are also discussed.

Effect of diets supplemented with different conjugated linoleic acid (CLA) isomers on protein expression in C57/BL6 mice.

BACKGROUND: The individual genetic variations, as a response to diet, have recently caught the attention of several researchers. In addition, there is also a trend to assume food containing beneficial substances, or to supplement food with specific compounds. Among these, there is the conjugated linoleic acid (CLA), which has been demonstrated to reduce fat mass and to increase lean mass, even though its mechanism of action is still not known. We investigated the effect of CLA isomers (CLA c9,t11 and CLA t10,c12) on the proteomic profile of liver, adipose tissue, and muscle of mouse, with the aim of verifying the presence of a modification in fat and lean mass, and to explore the mechanism of action. METHODS: C57/BL6 mice were fed for 2 months with different diets: (1) standard chow, (2) CLA c9,t11 diet, (3) CLA t10,c11 diet, (4) CLA isomers mixture diet, and (5) linoleic acid diet. The proteomic profile of liver, white adipose tissue, and muscle was investigated. Statistical significance of the spots with an intensity higher than twofold in expression compared to the control was tested using student's t test (two-tail). RESULTS: We found that both isomers modulate the proteomic profiles of liver, adipose tissue, and muscle by different mechanisms of action. Liver steatosis is mostly due to the isomer CLA t10,c12, since it alters the expression of lipogenetic proteins; it acts also reducing the adipose tissue and increasing fatty acid oxidation in muscle. Conversely, CLA c9,t11 has no relevant effects on liver and adipose tissue, but acts mostly on muscle, where it enhances muscular cell differentiation. CONCLUSIONS: Administration of CLA in humans has to be carefully personalized, since even considering the presence of a species-specific effect, adverse effects might occur on long-term supplementation. Here we demonstrated that, in mouse, CLA is effective in reducing fat mass, but it also induces liver steatosis. The increase of lean mass is linked to an induction of cell proliferation, which, on long-term supplementation, might also lead to adverse effects.

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.

Conjugated linoleic acid isomers modulate protein expression profile in rat hepatocytes.

Conjugated linoleic acid (CLA) is a polyunsaturated fatty acid, which has been recently proven to be effective in reducing body fat mass, but brings as a side effect, the liver enlargement due to an increased lipid content. The in vivo lipogenic activity has been suggested to be due to the reduction in fat mass and to the consequent metabolism of blood glucose to fatty acid in the liver rather than in the adipose tissue. We investigated the ability of CLA to directly induce steatosis by modulating the expression pattern of hepatic proteins involved in lipid metabolism. To avoid interferences derived from CLA metabolism by other tissues, we used the in vitro model of freshly isolated rat hepatocytes incubated in the presence of different CLA isomers. The direct effect of CLA on lipid accumulation in hepatocytes was demonstrated by the altered expression pattern of several proteins involved in lipid metabolism, as assessed by two-dimensional gel electrophoresis and confirmed by Western blotting analysis. The CLA isomer c9,t11 was most effective in modulating the protein expression profile.

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.

Eliminación del trazo gustativo tras la administración de MK-801 / Disruption of taste trace by MK-801 administration

La administración sistémica de antagonistas de NMDA produce una interrupción de la Aversión Condicionada al Sabor cuando el fármaco se inyecta antes de la presentación de los estímulos. Sin embargo, existen en la literatura muy pocos experimentos que analicen la relación entre el aprendizaje de aversión al sabor y la actividad de los receptores NMDA cuando los compuestos farmacológicos se inyectan por vía sistémica entre el Estímulo Condicionado (EC) y el Estímulo Incondicionado (EI), siendo además en estos casos los resultados más contradictorios. En este trabajo presentamos dos experimentos destinados a analizar si la administración de MK-801 (dizolcipina maleate) entre el EC y el EI produce una interrupción de la Aversión Condicionada al Sabor (Experimento 1), y si la introducción de una demora temporal entre el EC y la administración del MK-801 anula el efecto disruptivo de la droga sobre la aversión al sabor (Experimento 2). Los resultados revelan que el MK-801 produce la interrupción de la ACS cuando se inyecta entre el EC y el EI y que el efecto desaparece cuando se introduce un intervalo temporal entre la administración del fármaco y el EI. Estos resultados apuntan al importante papel que los receptores NMDA desempeñan en la codificación y consolidación del trazo de memoria para el sabor(AU)

Sistemic administration of NMDA antagonists induces a disruption of Conditioned Taste Aversion when the drug is administered before stimuli presentation. However, there is scarce evidence, and such evidence is contradictory, on the role of NMDA receptors on Conditioned Taste Aversion when the drugs are injected in the interval between the Conditioned Stimulus (CS) and the Unconditioned Stimulus (US). In this paper we describe two experiments designed to analyze whether MK-801 (dizolcipine maleate) administration during the interval between the CS and the US disrupts Conditioned Taste Aversion (Experiment 1), and whether the introduction of a delay between MK-801 administration and US presentation prevents such disruption (Experiment 2). The results show the predicted Conditioned Taste Aversion disruption when the drug was injected inmediately before the US, and normal Conditioned Taste Aversion when a delay was introduced between the NMDA antagonist and the US. These results support a relevant role of NMDA receptors in encoding and consolidation of the taste memory trace(AU)

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.

Interrupción del efecto de inhibición latente por la administración de MK-801 / Latent Inhibition disruption by MK-801 administration

Los receptores -metil-D-aspartato (NMDA) parecen estar implicados en el retraso en la adquisición de una asociación pavloviana tras la preexposición sin consecuencias al que se va a convertir en estímulo condicionado, efecto al que se suele denominar Inhibición Latente (IL). Concretamente, la administración de compuestos antagonistas en la fase de preexposición o en las fases de preexposición y condicionamiento produce un efecto disruptivo sobre la expresión de la IL cuando se utiliza un procedimiento de aversión condicionada al sabor. En este trabajo describimos tres experimentos que replican el efecto del MK-801 sobre la IL (Experimento 1) y que de muestran la persistencia de la influencia de la droga independientemente del número de ensayos de preexposición (Experimento 2), o de la intensidad del EC empleado (Experimento 3). Los resultados se interpretan en relación a los modelos psicológicos y farmacológicos relacionados con la investigación y el tratamiento clínico de diversos desordenes neuro-cognitivos (AU)

The-methyl-Daspartate (NMDA) receptors seem to be involved in the Latent Inhibition (LI) process -the retardation in the acquisition of a pavlovian association by previous preexposure to the to-be-conditioned stimulus-. Specifically, NMDA antagonist administration at preexposure, or at preexposure and conditioning stages using a conditioned taste aversion procedure has resulted in LI disruption. In this paper we describe three experiments that reproduce the disruptive effect of MK-801 on LI (Experiment 1), and demonstrate persistence of the drug effect irrespective of number of preexposure trials (Experiment 2) and CS intensity (Experiment 3). The results are discussed attending to those psychological and pharmacological models related to the research and treatment of neurocognitive disorders (AU)

Interrupción del efecto de inhibición latente por la administración de MK-801 / Latent inhibition disruption by MK-801 administration

Los receptores N-metil-D-aspartato (NMDA) parecen estar implicados en el retraso en la adquisición de una asociación pavloviana tras la preexposición sin consecuencias al que se va a convertir en estímulo condicionado, efecto al que se suele denominar Inhibición Latente (IL). Concretamente, la administración de compuestos antagonistas en la fase de preexposición o en las fases de preexposición y condicionamiento produce un efecto disruptivo sobre la expresión de la IL cuando se utiliza un procedimiento de aversión condicionada al sabor. En este trabajo describimos tres experimentos que replican el efecto del MK-801 sobre la IL (Experimento 1) y que demuestran la persistencia de la influencia de la droga independientemente del número de ensayos de preexposición (Experimento 2), o de la intensidad del EC empleado (Experimento 3). Los resultados se interpretan en relación a los modelos psicológicos y farmacológicos relacionados con la investigación yel tratamiento clínico de diversos desordenes neurocognitivos (AU)

N-methyl-Daspartate(NMDA) receptors seem to be involved in the Latent Inhibition(LI) process -the retardation in the acquisition of a pavlovian association by previous preexposure to the to-be-conditioned stimulus-. Specifically,NMDA antagonist administration at preexposure, or at preexposure and conditioning stages using a conditioned taste aversion procedure has resulted in LI disruption. In this paper we describe three experiments that reproduce the disruptive effect of MK-801 on LI (Experiment 1), and demonstrate persistence of the drug effect irrespective of number of preexposure trials (Experiment 2) and CS intensity (Experiment 3). The results are discussed attending to those psychological and pharmacological models related to the research and treatment of neurocognitive disorders (AU)

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.

Nipple leiomyoma in man: a case report.

We describe a rare case of a man, 38 year old, with a nipple leiomyoma, and report the presentation as a small nodule of the areola spreading the nipple, the symptoms, the clinical signs, the treatment that includes a complete excision; free margins should be histologically established to prevent recurrence.

Aprendizaje sabor-sabor en la adquisición de preferencias gustativas / Taste-taste learning on the adquisition of the flavor preferences

En este trabajo, en el que se emplean ratas como sujetos experimentales, ponemos a prueba la hipótesis según la cual el aprendizaje de preferencias adquiridas con respecto a sabores sin consecuencia nutritivas post-ingesta se rige por mecanismos de condicionamiento clásico (por ej., Fedorchak, 1997). Con este objetivo llevamos a cabo dos experimentos. En el Experimento 1 utilizamos un diseño entre-sujetos para analizar el desarrollo de preferencias gustativas condicionadas hacia un sabor inicialmente no preferido (ácido cítrico). Para ello, se emparejó el ácido cítrico con otro saborde demostrado valor hedónico positivo (sacarina) que carece de poder calórico (Capaldi, Hunter y Lyn, 1997). En el segundo experimento comprobamos la posible naturaleza asociativa de este aprendizaje devaluando el valor reforzante de la sacarina mediante su emparejamiento con una inyección deCloruro de Litio. En general, los resultados mostraron un efecto de preferencia condicionada hacia el ácido cítrico tras su emparejamiento con la sacarina. Esta preferencia condicionada fue eliminada tras devaluar el valor reforzante de la sacarina mostrando que el mecanismo responsable de la asociación sabor-sabor es de naturaleza asociativa (AU)

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.