https://hdl.handle.net/10481/62138 Fri, 17 Apr 2026 03:27:21 GMT 2026-04-17T03:27:21Z https://hdl.handle.net/10481/92116 Identification of Differentially Expressed MicroRNAs in the Rat Hippocampus during Adolescence through an Epigenome-Wide Analysis Vázquez de Ágredos Martín Gil, Ana; Rovira Lorente, Paula; Gutiérrez Martínez, Blanca; Gámiz Ruiz, Fernando; Gallo Torres, Milagros Introduction: Epigenetic mechanisms involving microRNAs (miRNAs) play a fundamental role in many biological processes, particularly during prenatal and early postnatal development. Their role in adolescent brain development, however, has been poorly described. The present study aimed to explore miRNA expression in the hippocampus during adolescence compared to adulthood in rats. Method: The brains of female and male Wistar rats were extracted, and the hippocampus was freshly dissected at postnatal day 41 (adolescence) and postnatal day 98 (adulthood). An epigenome-wide analysis was conducted to identify the miRNAs significantly expressed in adolescence compared to adulthood. Additionally, target genes of such miRNAs were considered to perform an exploratory Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Results: We identified 16 differentially expressed miRNAs in adolescent male rats compared with adult male rats and 4 differentially expressed miRNAs in adolescent females compared with adult females. Enrichment analysis reinforced that the target genes found are related to neurodevelopmental processes such as cell proliferation, cell migration, and nervous system development. Conclusion: Our findings suggest a complex pattern of miRNA expression during adolescence, which differs from that in adulthood. The differential expression of miRNA in the hippocampus during adolescence may be associated with the late developmental changes occurring in this brain region. Furthermore, the observed sex differences in miRNA expression patterns indicate potential sexual differentiation in hippocampal development. Further comprehensive investigations are needed to elucidate the roles of miRNA in normal brain development. This study was funded by the research projects PID2020-114269GB-I00 (MCIN/AEI/10.13039/501100011033), BSEJ.514.UGR20 (FEDER, Junta de Andalucía, Spain), “Instituto de Salud Carlos III,” project PI18/00467 (co-funded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”), and a predoctoral fellowship to AV-Á (FPU18/05012, MIU, Spain). https://hdl.handle.net/10481/92116 https://hdl.handle.net/10481/92113 Adolescent alcohol exposure modifies adult anxiety-like behavior and amygdala sensitivity to alcohol in rats: Increased c-Fos activity and sex-dependent microRNA-182 expression Vázquez de Ágredos Martín Gil, Ana; Valero, Marta; Aparicio-Mescua, Teresa; García-Rodríguez, Raquel; Gámiz Ruiz, Fernando; Gallo Torre, Milagros Adolescent binge alcohol drinking is a serious health concern contributing to adult alcohol abuse often associated with anxiety disorders. We have used adolescent intermittent ethanol (AIE) administration as a model of binge drinking in rats in order to explore its long-term effect on the basolateral amygdala (BLA) responsiveness to alcohol and anxiety-like behavior. AIE increased the number of BLA c-Fos positive cells in adult Wistar rats and anxiety-like behavior assessed by the open field test (OFT). Additionally, in adult female rats receiving AIE BLA over expression of miR-182 was found. Therefore, our results indicate that alcohol consumption during adolescence can lead to enduring changes in anxiety-like behavior and BLA susceptibility to alcohol that may be mediated by sex-dependent epigenetic changes. These results contribute to understanding the mechanisms involved in the development of alcohol use disorders (AUD) and anxiety-related disorders. https://hdl.handle.net/10481/92113 https://hdl.handle.net/10481/90517 Perceptual Learning After Rapidly Alternating Exposure to Taste Compounds: Assessment With Different Indices of Generalization Sánchez Plazas, Jesús; Dwyer, Dominic; Honey, Robert; Brugada Sauras, Isabel de Exposure to two similar stimuli (AX and BX; e.g., two tastes) reduces the extent to which a conditioned response later established to BX generalizes to AX. This example of perceptual learning is more evident when AX and BX are exposed in an alternating manner (AX, BX, AX, BX,. . ..) than when AX and BX AQ: 4 occurs in separate blocks (e.g., AX, AX,..BX, BX,..). We examined in male rats (N = 126) the impact of rapid alternation to AX and BX on generalization of a taste aversion from BX to AX. Experiment 1 showed that such alternating presentations (with 5-min intervals between AX and BX) reduced generalization relative to blocked exposure; but only as assessed by consumption levels and not by lick cluster size (an index of hedonic reactions). Experiment 1 also showed that the nature of exposure did not affect how A influenced performance to a novel conditioned taste, Y. Experiment 2 replicated the pattern of results involving the different influences of rapidly alternating and blocked exposure on generalization from BX to AX, and showed that this effect was only evident when rats received access to water during the 5-min intervals between AX and BX. These results reinforce parallels between perceptual learning effects in rats and humans, both at empirical and theoretical levels. https://hdl.handle.net/10481/90517 https://hdl.handle.net/10481/90515 Intermixed Rapid Exposure to Similar Stimuli Reduces the Effective Salience of Their Distinctive Features Sánchez, Jesús; González Gómez, Ana; Brugada Sauras, Isabel de Intermixed exposure to two similar stimuli, e.g., AX and BX, improves subsequent discrimination between them compared to blocked exposure (the intermixed/blocked effect). Salience modulation models, developed mainly from research with nonhuman animals and exposure to widely spaced similar stimuli, explain this effect in terms of increased salience of the unique elements, A and B. Conversely, results from experiments initially conducted with humans and exposure to close spaced similar stimuli have led to the suggestion that it is the development of well-unitized representations of unique elements that leads to better discrimination, leaving the unique elements with less effective salience. The experiments carried out here aim to replicate the intermixed/blocked effect in rats using an exposure procedure with rapid succession between stimuli and to assess the effective salience of unique elements. In Experiment 1, an aversion to a new flavor, Y, was conditioned and then an external inhibition test with AY was given. In Experiment 2, an aversion to A was conditioned and its extinction was measured on unreinforced trials. In Experiment 3, an aversion to AY was conditioned and the associated aversion to Y was measured. We found after rapid intermixed preexposure a reduction in generalization from the aversive Y element to the compound AY (Experiment 1) as well as a reduction in A’s salience (Experiments 2 and 3) compared to the effects of blocked preexposure. The results are discussed in terms of the various mechanisms underlying perceptual learning, which appear to depend on the details of the task. https://hdl.handle.net/10481/90515 https://hdl.handle.net/10481/90509 Does drinking saccharin weaken an association of sweet with calories? Pre-exposure effects in flavor preference learning González, Ana; Boakes, Robert; Hall, Geoffrey; Brugada Sauras, Isabel de The main aim of this experiment was to examine the claim that exposure to non-nutritive sweeteners weakens the formation of a sweet-calorie association. Three groups of food-deprived rats received training in which they drank an almond-flavored maltodextrin and saccharin solution. A final test phase assessed their preference for almond. The groups differed in preexposure prior to training. One was pre-exposed to saccharin, one to saccharin plus maltodextrin, and the third, control condition, received only water at this stage. When the rats continued under food deprivation for the test phase, the group exposed to the compound (saccharin plus maltodextrin) showed a weaker preference than the other two groups, while those pre-exposed to saccharin showed as strong a preference as the controls. When the test was conducted with the rats no longer food-deprived, only the water group showed a strong preference. These results support the proposal that rats can form both flavor-flavor and flavor-nutrient associations, expression of which will depend on motivational state. They did not find support for the suggestion that prior exposure to a non-nutritive sweetener can enhance subsequent learning about the nutritive properties of a sweet food. https://hdl.handle.net/10481/90509