Conditioned inhibition in preweanling rats.

Inhibitory conditioning is a very well established phenomenon in associative learning that has been demonstrated in both humans and adult animals. But in spite of the fact that this topic has generated much empirical and theoretical work, there are no published studies assessing inhibitory learning during the early ontogeny of the rat. In this study we test the possibility of finding conditioned inhibition in infant rats (Day 10) using a conditioned taste aversion procedure. We tested whether the consumption of saccharin (A) was reduced when paired with a LiCl injection compared to the presentation of saccharin in compound with a lemon odor (AX) without any aversive consequence. After training, retardation, and summation tests were conducted in order to evaluate the inhibitory properties of the lemon odor (X). The results of this study showed that in male pups, after conditioned inhibition training, stimulus X passed both retardation and summation tests. These results indicate that conditioned inhibition can be established in the early development of the rat, suggesting that animals at this stage of ontogeny have the capacity to acquire and to express inhibitory conditioning, although this effect appears to be sex-dependent.

Latent inhibition and facilitation of conditioned taste aversion in preweanling rats.

Early in ontogeny, taste preexposure has been found to induce latent inhibition as well as produce a facilitation of conditioned taste aversion (CTA). In this study, the effect of taste preexposure on CTA was investigated in 13-14 day old rats as a function of taste preexposure (0, 1, or 3 trials) and unconditioned stimulus intensity (LiCl: 0, 0.15, or 0.30 M). After one conditioning trial, with the low intensity US, an aversion was only observed after taste preexposure (facilitation). When using the strong US, an aversion was found without preexposure while latent inhibition was observed with 3 preexposure trials. In conclusion, stimulus preexposure can either facilitate conditioning or produce latent inhibition in infant rats, depending on the amount of stimulus preexposure and the intensity of the US.

Exposure to ethanol on prenatal days 19-20 increases ethanol intake and palatability in the infant rat: involvement of kappa and mu opioid receptors.

Prenatal exposure to ethanol on gestation Days 19-20, but not 17-18, increases ethanol acceptance in infant rats. This effect seems to be a conditioned response acquired prenatally, mediated by the opioid system, which could be stimulated by ethanol's pharmacological properties (mu-opioid receptors) or by a component of the amniotic fluid from gestation-day 20 (kappa-inducing factor). The latter option was evaluated administering non-ethanol chemosensory stimuli on gestation Days 19-20 and testing postnatal intake and palatability. However, prenatal exposure to anise or vanilla increased neither intake nor palatability of these tastants on postnatal Day 14. In experiment 2, the role of ethanol's pharmacological effect was tested by administering ethanol and selective antagonists of mu and kappa opioid receptors prenatally. Blocking the mu-opioid receptor system completely reversed the effects on intake and palatability, while antagonizing kappa receptors only partially reduced the effects on palatability. This suggests that the pharmacological effect of ethanol on the fetal mu opioid system is the appetitive reinforcer, which induces the prenatally conditioned preference detected in the preweanling period.

Small for Gestational Age Moderate to Late Preterm Children: A Neuropsychological Follow-up.

Determine whether SGA constitutes a neurodevelopmental risk-factor of MLP, exploring if potential developmental difficulties at toddlerhood persist and are related to school-age performance. 109 SGA and 109 adequate for gestational age MLP children were evaluated at 2 and at 6.5 y.o. SGA children obtained poorer results in several areas at both timepoints; and their development at toddlerhood strongly correlated with only some results at school-age. SGA confers vulnerability to MLP, evolving from global/unspecific difficulties in toddlerhood to a domain-specific profile (attentional/dysexecutive) at 6.5. Findings claim the need for neuropsychological follow-up in MLP to identify emerging difficulties.

Prenatal Alcohol Exposure as a Case of Involuntary Early Onset of Alcohol Use: Consequences and Proposed Mechanisms From Animal Studies.

Prenatal alcohol exposure has been found to be an important factor determining later consumption of this drug. In humans, despite the considerable diversity of variables that might influence alcohol consumption, longitudinal studies show that maternal alcohol intake during gestation is one of the best predictors of later alcohol use from adolescence to young adulthood. Experimental studies with animals also provide abundant evidence of the effects of prenatal alcohol exposure on later alcohol intake. In addition to increased consumption, other effects include enhanced palatability and attractiveness of alcohol flavor as well as sensitization to its sensory and reinforcing effects. Most of these outcomes have been obtained after exposing rats to binge-like administrations of moderate alcohol doses during the last gestational period when the fetus is already capable of detecting flavors in the amniotic fluid and learning associations with aversive or appetitive consequences. On this basis, it has been proposed that one of the mechanisms underlying the increased acceptance of alcohol after its prenatal exposure is the acquisition (by the fetus) of appetitive learning via an association between the sensory properties of alcohol and its reinforcing pharmacological effects. It also appears that this prenatal appetitive learning is mediated by the activation of the opioid system, with fetal brain acetaldehyde playing an important role, possibly as the main chemical responsible for its activation. Here, we review and analyze together the results of all animal studies testing these hypotheses through experimental manipulation of the behavioral and neurochemical elements of the assumed prenatal association. Understanding the mechanisms by which prenatal alcohol exposure favors the early initiation of alcohol consumption, along with its role in the causal pathway to alcohol disorders, may allow us to find strategies to mitigate the behavioral effects of this early experience with the drug. We propose that prenatal alcohol exposure is regarded as a case of involuntary early onset of alcohol use when designing prevention policies. This is particularly important, given the notion that the sooner alcohol intake begins, the greater the possibility of a continued history of alcohol consumption that may lead to the development of alcohol use disorders.

The Role of Acetaldehyde in the Increased Acceptance of Ethanol after Prenatal Ethanol Exposure.

Recent studies show that acetaldehyde, the first metabolite in the oxidation of ethanol, can be responsible for both, the appetitive and the aversive effects produced by ethanol intoxication. More specifically, it has been hypothesized that acetaldehyde produced in the periphery by the liver is responsible for the aversive effects of ethanol, while the appetitive effects relate to the acetaldehyde produced centrally through the catalase system. On the other hand, from studies in our and other laboratories, it is known that ethanol exposure during the last gestational days (GD) consistently enhances the postnatal acceptance of ethanol when measured during early ontogeny in the rat. This increased liking of ethanol is a conditioned appetitive response acquired by the fetus by the association of ethanol's flavor and an appetitive reinforcer. Although this reinforcer has not yet been fully identified, one possibility points to acetaldehyde produced centrally in the fetus as a likely candidate. This hypothesis is supported by data showing that very early in the rat's ontogeny brain catalases are functional, while the liver's enzymatic system is still immature. In this study, rat dams were administered on GD 17-20 with water or ethanol, together with an acetaldehyde-sequestering agent (D-penicillamine). The offspring's responses to ethanol was then assessed at different postnatal stages with procedures adequate for each developmental stage: on day 1, using the "odor crawling locomotion test" to measure ethanol's odor attractiveness; on day 5, in an operant conditioning procedure with ethanol as the reinforcer; and on day 14 in an ethanol intake test. Results show that the absence of acetaldehyde during prenatal ethanol exposure impeded the observation of the increased acceptance of ethanol at any age. This seems to confirm the crucial role of acetaldehyde as a reinforcer in the appetitive learning occurring during prenatal ethanol exposure.

Prenatal exposure to vanilla or alcohol induces crawling after these odors in the neonate rat: The role of mu and kappa opioid receptor systems.

Rat fetuses can perceive chemosensory stimuli derived from their mother's diet, and they may learn about those stimuli. In previous studies we have observed that prenatal exposure to alcohol during the last days of gestation increases the acceptance and liking of an alcohol flavor in infant and adolescent rats. While these results were not found after prenatal exposure to vanilla, cineole or anise, suggesting that the pharmacological properties of alcohol, mediated by the opioid system, underlie the effects observed with this drug. Considering that other studies report enhanced acceptance of non-alcohol flavors experienced prenatally when subjects were tested before infancy, we explore the possibility of observing similar results if testing 1-day old rats exposed prenatally to vanilla. Using an "odor-induced crawling" testing procedure, it was observed that neonates exposed prenatally to vanilla or alcohol crawl for a longer distance towards the experienced odor than to other odors or than control pups. Blocking mu, but not kappa opioid receptors, reduced the attraction of vanilla odor to neonates exposed to vanilla in utero, while the response to alcohol in pups exposed prenatally to this drug was affected by both antagonists. Results confirm that exposure to a non-alcohol odor enhances postnatal responses to it, observable soon after birth, while also suggesting that the mu opioid receptor system plays an important role in generating this effect. The results also imply that with alcohol exposure, the prenatal opioid system is wholly involved, which could explain the longer retention of the enhanced attraction to alcohol following prenatal experience with the drug.

[Cognitive performance and quality of life in multiple sclerosis in Gipuzkoa]. / Rendimiento cognitivo y calidad de vida de la esclerosis múltiple en Gipuzkoa.

INTRODUCTION: Cognitive impairment and the presence of depressive symptoms, which are commonly found in patients with multiple sclerosis, affect the patients' quality of life. AIM. To describe the quality of life, cognitive compromise and levels of depression, in relation to other clinical variables, in patients with multiple sclerosis in the province of Gipuzkoa. PATIENTS AND METHODS: A total of 114 patients were submitted to neuropsychological evaluation. The MSQoL-54 and Beck's Depression Inventory were applied to evaluate the quality of life and levels of depression. Three main analyses were performed: a comparison of cognitive performance among subtypes, an analysis of the correlation among clinical, neuro-psychological and quality of life variables, and an analysis of the effects of gender on cognitive performance. RESULTS: A neuropsychological pattern is found in multiple sclerosis that is characterised by a slowing of the processing of information and attentional difficulties. Quality of life is related with depressive syndromes and with overall cognitive performance but not with clinical factors such as the rate of attacks or the length of time the disease lasts. The data confirm the existence of poorer cognitive performance in males, above all in terms of verbal auditory memory. CONCLUSIONS: Gender is presented as a factor that modulates the impact of the disease on cognitive performance, which reinforces the interest in conducting studies that clarify the origin of such differences. Furthermore, the quality of life displays a greater relationship with the degree of adaptation to the disease than with its symptoms.

TITLE: Rendimiento cognitivo y calidad de vida de la esclerosis multiple en Gipuzkoa.Introduccion. El deterioro cognitivo y la presencia de sintomas depresivos, comunes en los pacientes con esclerosis multiple, inciden en la calidad de vida de los pacientes. Objetivo. Describir la calidad de vida, la afectacion cognitiva y los niveles de depresion, en relacion con otras variables clinicas, en los pacientes con esclerosis multiple de la provincia de Gipuzkoa. Pacientes y metodos. Se evaluo neuropsicologicamente a 114 pacientes. Se incluyeron el MSQoL-54 y el inventario de depresion de Beck para evaluar la calidad de vida y los niveles de depresion. Se emprendieron tres analisis principales: comparacion del rendimiento cognitivo entre subtipos, analisis de correlacion entre variables clinicas, neuropsicologicas y de calidad de vida, y analisis sobre los efectos del genero en el rendimiento cognitivo. Resultados. Se halla en la esclerosis multiple un patron neuropsicologico caracterizado por enlentecimiento en el procesamiento de la informacion y dificultades atencionales. La calidad de vida se relaciona con sintomas depresivos y con el rendimiento cognitivo global pero no con factores clinicos como la tasa de brote o la duracion de la enfermedad. Los datos confirman un peor rendimiento cognitivo en los hombres, sobre todo en la memoria auditiva verbal. Conclusiones. El genero se presenta como un factor modulador en el impacto de la enfermedad sobre el rendimiento cognitivo, que refuerza el interes de estudios que clarifiquen el origen de dichas diferencias. Ademas, la calidad de vida muestra una mayor relacion con la adaptacion a la enfermedad que con sus sintomas.

MC4-R signaling within the nucleus accumbens shell, but not the lateral hypothalamus, modulates ethanol palatability in rats.

The Melanocortin (MC) system is one of the crucial neuropeptidergic systems that modulate energy balance. The roles of endogenous MC and MC-4 receptor (MC4-R) signaling within the hypothalamus in the control of homeostatic aspects of feeding are well established. Additional evidence points to a key role for the central MC system in ethanol consumption. Recently, we have shown that nucleus accumbens (NAc), but not lateral hypothalamic (LH), infusion of a selective MC4-R agonist decreases ethanol consumption. Given that MC signaling might contribute to non-homeostatic aspects of feeding within limbic circuits, we assessed here whether MC4-R signaling within the NAc and the lateral hypothalamus (LH) alters normal ingestive hedonic and/or aversive responses to ethanol in rats as measured by a taste reactivity test. Adult male Sprague-Dawley rats were given NAc- or LH- bilateral infusion of the selective MC4-R agonist cyclo (NH-CH(2)-CH(2)-CO-His-D-Phe-Arg-Trp-Glu)-NH(2) (0, 0.75 or 1.5µg/0.5µl/site) and following 30 min, the animals received 1 ml of ethanol solution (6% w/v) intraoral for 1 minute and aversive and hedonic behaviors were recorded. We found that NAc-, but not LH-administration, of a selective MC4-R agonist decreased total duration of hedonic reactions and significantly increased aversive reactions relative to saline-infused animals which support the hypothesis that MC signaling within the NAc may contribute to ethanol consumption by modulating non-homeostatic aspects (palatability) of intake.