No abstract

In summary, using a short period of ethanol exposure and a brief deprivation period the results revealed a direct relationship between chronological age and propensity to consume alcohol, being the adolescence a transition period from the infant to the adult pattern of alcohol consumption. Preadolescent animals showed the highest ethanol consumption level. The ADE was only found in adult animals for both alcohol consumption and preference, whereas adolescents showed an ADE only for preference. No effect of sex was detected in any phase of the experiment.

In a pair of experiments, we have compared the ability of changes of place (Exp. 1) and changes of time of day (Exp. 2) to separately modulate learned saline-aversion memory phenomena in rats. Neither a spatial nor a temporal change disrupted latent inhibition using the present behavioral procedure. However, pre-exposure to the taste increased the contextual control of the learned aversion expression. The aversion reappeared in the place or at the time of conditioning after extinction in a different context. The results indicate that environmental and temporal contexts can independently, but similarly modulate taste aversion learning.Context is an often loosely defined term, which in neuroscience is becoming more common, especially with the current interest to investigate the neural bases of episodic memory in humans (Nadel et al 1985;Schacter and Tulving 1994) and to search for equivalent memory phenomena in nonhuman animals (Clayton and Dickinson 1998;Aggleton and Brown 1999). Whereas rats readily associate tastes of substances with their visceral consequences (García and Koelling 1966;García et al. 1968;Bures et al. 1998;Bernstein 1999), contextual cues also modulate conditioned taste aversions (CTA), because the context specificity, both of the expression (Boakes et al. 1997;Archer et al. 1979Archer et al. , 1980Jarbe et al. 1986;Puente et al. 1988;Bonardi et al. 1990;Loy et al. 1993) and extinction (Rosas and Bouton 1997;Archer et al. 1979) of a learned aversion, and of the latent inhibition (LI) of CTA (Rudy et al. 1977;Hall and Channell 1986) has been reported. In CTA studies, context frequently refers to a particular place that may combine a variety of external environmental cues. However, a broad definition of context may include not only external, but also internal, background cues and a sense of time (Bouton 1993;Pearce and Bouton 2001). Very few of the above-cited studies reporting context modulation of CTA have included the time of day as part of the context, either purposely (Rosas and Bouton 1997) or as the outcome of applying two daily drinking sessions (Hall and Channell 1986;Bonardi et al. 1990). Moreover, although the possibility that the time of day may itself form a context is supported by a recent report showing a time-of-day-dependent expression of the behavioral sensitization to amphetamine (Arvanitogiannis et al. 2000), to our knowledge, no study has explored the ability of the time of day to modulate CTA independently of the spatial context.In the present experiments, we specifically examine whether spatial (Exp. 1) and temporal (Exp. 2) contextual cues separately modulate learned saline-aversion memory phenomema. In Experiment 1, two different sized and shaped cages were used as contexts (Fig. 1). The environments differed in location, geometry, visual, auditory, and tactile cues. In Experiment 2, two different times during the illumination cycle were used as temporal contexts. To differentiate them as much as possible, morning (10:00) and evening (20:00) drinking sessions were used. E...

Recent clinical findings support the notion that the progressive deterioration of cholesterol homeostasis is a central player in Alzheimer's disease (AD). Epidemiological studies suggest that high midlife plasma total cholesterol levels are associated with an increased risk of AD. This paper reports the plasma cholesterol concentrations, cognitive performance, locomotor activity and neuropathological signs in a murine model (transgenic mice expressing apoB100 but knockout for the LDL receptor [LDLR]) of human familial hypercholesterolaemia (FH). From birth, these animals have markedly elevated LDL-cholesterol and apolipoprotein B100 (apoB100) levels. These transgenic mice were confirmed to have higher plasma cholesterol concentrations than wild-type mice, an effect potentiated by aging. Further, 3-month-old transgenic mice showed cholesterol (total and fractions) concentrations considerably higher than those of 18-month-old wild-type mice. The hypercholesterolaemia of the transgenic mice was associated with a clear locomotor deficit (as determined by rotarod, grip strength and open field testing) and impairment of the episodic-like memory (determined by the integrated memory test). This decline in locomotor activity and cognitive status was associated with neuritic dystrophy and/or the disorganization of the neuronal microtubule network, plus an increase in astrogliosis and lipid peroxidation in the brain regions associated with AD, such as the motor and lateral entorhinal cortex, the amygdaloid basal nucleus, and the hippocampus. Aortic atherosclerotic lesions were positively correlated with age, although potentiated by the transgenic genotype, while cerebral β-amyloidosis was positively correlated with genetic background rather than with age. These findings confirm hypercholesterolaemia as a key biomarker for monitoring mild cognitive impairment, and shows these transgenic mice can be used as a model for cognitive and psycho-motor decline.

Rats use time-of-day cues to modulate learned taste aversion memories. If adult rats are accustomed to drinking saline in the evening and they receive a lithium chloride injection after drinking saline in the morning, they form a stronger aversion to saline than rats that were conditioned after drinking saline at the familiar time. The difference indicated that the rats formed segregated representations of saline taste and the time of day the saline was consumed. This was inferred because the modulation of learning by time of day was observed when the aversions were tested at the familiar evening drinking time. If the rats had formed a compound representation of saline taste and the time of day it was consumed, the opposite pattern of differences would be expected. We used this modulation of learning by time of day to assay whether aged rats have an impaired ability to form segregated representations of experience. We find that aged rats had similar saline aversions if they were conditioned at either the familiar or the unfamiliar time of day. Furthermore, dorsal hippocampal lesions affecting also the overlying parietal cortex in the aged rats caused greater saline aversions if the rats were conditioned after drinking saline at the familiar time of day. This indicated that aged rats are aware of the time of day but after the lesion, they act as if they do not segregate saline taste from the time of day it was consumed. The results suggest that the ability to form segregated representations of a complex experience is impaired in aging and abolished by hippocampal lesions.