Biology subjects

Maldonado-Devincci, A. M.

Publications and source records attributed to Maldonado-Devincci, A. M..

7 recordsLinked to original sources

bioRxiv2026

Chronic Intermittent Ethanol Exposure Produces Sex- and Tissue-Specific Metabolomic Signatures Across the Gut-Liver Axis in Adult Mice

Alcohol misuse leads to a range of health complications and induces various metabolic perturbations that impacts multiple physiological systems, including the cardiovascular system, liver, and gut microbiota. However, limited research has been reported on these metabolic profile changes, particularly using models of alcohol dependence such as after chronic intermittent ethanol (CIE) vapor exposure. This study investigated CIE-induced metabolomic alterations of CIE were investigated using fecal, liver, and serum samples of adult male and female C57BL/6J mice following 72 hr withdrawal. Significant metabolite changes were observed in both fecal and liver extracts and these changes were sex-specific. Both liver and fecal metabolites had systematic changes, while blood serum influences were limited after CIE. Female fecal samples showed higher metabolite perturbations than male samples according to PCA studies. The female samples showed significant butyrate downregulation and acetate upregulation, which are critical microbial products as beneficial microbe cell energy sources and influence intestinal absorption in the host. In addition, the female fecal samples showed significant downregulation of branched-chain amino acids including leucine, isoleucine, and valine, while male samples showed downregulation of glucose and taurine, with upregulated phenylalanine and tyrosine. In contrast, in the liver study, phenylalanine and tyrosine were upregulated while taurine was downregulated in females. Both sexes showed downregulation of liver glycine and glucose. These data indicate that CIE induces sex-specific metabolic perturbations in the mouse liver and fecal metabolome, and have implications for guy disturbances and liver damage observed following alcohol dependence. This study provides potential targets for future examination of mechanisms and treatment approaches for alcohol dependence.

neuroscience↗

bioRxiv2025

Novel reactivity phenotype mediates long-term consequences of cocaine exposure during adolescence and adulthood in male Sprague-Dawley rats.

Individual differences in novelty seeking behavior often predict locomotor responses to psychomotor stimulants, an effect that may have a lasting impact throughout adolescence. The present study examined the role of novel reactivity phenotype on locomotor responses to repeated cocaine exposure during adolescence and adulthood in male rats. Prior to drug exposure, reactivity to a novel object was measured and animals were separated into low responders (LR) and high responders (HR). Cocaine was administered daily (0 or 20 mg/kg, i.p.) for 12 consecutive days, and behavior recorded on days 1, 6, and 12. After 28 days without drug, rats were challenged with cocaine (20 mg/kg) and behavior was assessed. Novel reactivity phenotype had a dramatic role in adolescents acute responsiveness to cocaine. HR adolescents exhibited a robust increase in sensitivity to acute administration of 20 mg/kg cocaine. However, following repeated cocaine exposure, both LR and HR adults displayed a marked increase in cocaine-induced locomotor activity, whereas the change in behavioral responsiveness in LR and HR adolescents was not as dramatic. During the cocaine challenge trial, LR that were exposed to 20 mg/kg cocaine during adolescence showed the highest cocaine-induced responsiveness compared to their saline-exposed and adult-exposed counterparts. Overall, these data indicate that novel reactivity phenotype and age of initial cocaine exposure are intricately involved in the long-term behavioral effects of cocaine. Thus, novel reactivity phenotype may predispose cocaine-using adolescents to continue drug-seeking behavior and potential abuse. HighlightsO_LINovel reactivity is higher in adolescents compared to adults C_LIO_LIAdolescents show greater acute cocaine-induced activity compared to adults C_LIO_LIHigh responding adolescents show robust acute cocaine-induced activity C_LIO_LILow responding adolescents show lasting changes in cocaine activity in adulthood C_LI

neuroscience↗

bioRxiv2025

Developmental Differences in Novelty Reactivity in Adolescent and Adult Male and Female Rats

Adolescence is a time of high-risk behavior and increased exploration. This developmental period is marked by a greater probability of initiating drug use and is associated with an increased risk to develop addiction and dependency in adulthood. Human adolescents are predisposed toward an increased likelihood of risk taking behaviors, including drug use or initiation. The purpose of the study was to examine differences in developmental risk-taking behaviors. Adolescent and adult animals were exposed to a novel stimulus in a familiar environment to assess impulsive behaviors, novelty preference and exploratory behaviors. Adolescent animals had greater novelty-induced locomotor activity, greater novelty preference, and showed higher approach and exploratory behaviors compared to preadolescent and adult animals. These data support the notion that adolescents may be predisposed toward sensation seeking and consequently are more likely to engage in risk taking behaviors, such as drug use initiation.

neuroscience↗

bioRxiv2025

Adolescent intermittent ethanol exposure induces sex-specific and time-dependent changes in affective behaviors and metabolomic profiles.

Given the adverse effects of adolescent binge alcohol consumption in humans, the present work explores the lasting behavioral and metabolomic impacts following adolescent binge ethanol exposure. Here we determine short- and long-term changes in affective behaviors and metabolomic profiles in male and female adolescent binge ethanol-exposed mice. Male and female C57BL/6J mice were exposed to adolescent intermittent ethanol (AIE) as a model of binge ethanol exposure using intermittent vapor inhalation from postnatal day (PND) 28-42. Mice were tested in a battery of behavioral tests and metabolomic analyses were conducted following short-term and long-term withdrawal from AIE exposure. Mice were tested for affective behaviors using the open field test (OFT), the light/dark test (LDT), and the tail suspension test (TST) one week following AIE exposure from PND 49-53 and again from PND 91-95. Serum samples were collected on PND 43, corresponding to 24 hours after the last exposure, fecal samples were collected during each OFT, and liver samples were collected approximately 80 days after AIE exposure for metabolomic analysis. We show modest incubation of behavioral differences in anxiety-like behavior in males after adolescent binge ethanol exposure; an effect that was absent in female mice. In contrast, metabolomic differences in male mice that were more pronounced shortly after adolescent binge ethanol exposure waned as time progressed since last exposure. Male mice appear to be more susceptible to the persistent changes in adolescent binge ethanol exposure that varies over time. It is possible that short-term metabolomic changes may predict long-term behavioral changes in affective behaviors. Contribution to the field statementAdolescent binge alcohol exposure causes long-lasting changes in behavior, however the underlying biology mediating these changes have not readily been assessed in a sex-specific manner. Metabolomic assays are a powerful tool that can be used as biomarkers to determine changes in biological pathways that are linked to specific behavioral phenotypes. Here we explored the relationship between adolescent binge alcohol exposure, changes in anxiety-like behavior, and metabolomic profiles in male and female C57BL/6J mice. We find robust changes in metabolomic profiles following short-term withdrawal in male mice exposed to binge alcohol during adolescence. We also see modest changes in anxiety-like behavior following long-term withdrawal. Although female mice did not show any robust changes in anxiety-like behavior nor global changes in metabolomic profiles, in both sexes we do observe persistent changes in some amino acids, which may serve as specific biomarkers associated with changes in alcohol-induced behavioral changes. These data add to the field by conducting a novel longitudinal study following male and female mice from adolescence to early adulthood and measuring physiological biomarkers (metabolomics) coupled with behavioral changes following binge ethanol exposure.

neuroscience↗

bioRxiv2023

Adolescent Intermittent Ethanol Exposure Alters Exploratory and Affective Behaviors, and Cerebellar Grin2B Expression in Adulthood

Binge drinking is one of the most common patterns (more than 90%) of alcohol consumption by young people. During adolescence, the brain undergoes maturational changes that influence behavioral control and affective behaviors, such as cerebellar brain volume and function in adulthood. We investigated long-term impacts of adolescent binge ethanol exposure on affective and exploratory behaviors and cerebellar gene expression in adult male and female mice. Further, the cerebellum is increasingly recognized as a brain region integrating a multitude of behaviors that span from the traditional primary sensory-motor to affective functions, such as anxiety and stress reactivity. Therefore, we investigated the persistent effects of adolescent intermittent ethanol (AIE) on exploratory and affective behaviors and began to elucidate the role of the cerebellum in these behaviors through excitatory signaling gene expression. We exposed C57BL/6J mice to AIE or air (control) vapor inhalation from postnatal day 28-42. After prolonged abstinence (>34 days), in young adulthood (PND 77+) we assessed behavior in the open field, light/dark, tail suspension, and forced swim stress tests to determine changes in affective behaviors including anxiety-like, depressive-like, and stress reactivity behavior. Excitatory signaling gene mRNA levels of fragile X messenger ribonucleoprotein (FMR1), glutamate receptors (Grin2a, Grin2B and Grm5) and excitatory synaptic markers (PSD-95 and Eaat1) were measured in the cerebellum of adult control and AIE-exposed mice. AIE-exposed mice showed decreased exploratory behaviors in the open field test (OFT) where both sexes show reduced ambulation, however only females exhibited a reduction in rearing. Additionally, in the OFT, AIE-exposed females also exhibited increased anxiety-like behavior (entries to center zone). In the forced swim stress test, AIE-exposed male mice, but not females, spent less time immobile compared to their same-sex controls, indicative of sex-specific changes in stress reactivity. Male and female AIE-exposed mice showed increased Grin2B (Glutamate Ionotropic Receptor NMDA Type Subunit 2B) mRNA levels in the cerebellum compared to their same-sex controls. Together, these data show that adolescent binge-like ethanol exposure altered both exploratory and affective behaviors in a sex-specific manner and modified cerebellar Grin2B expression in adult mice. This indicates the cerebellum may serve as an important brain region that is susceptible to long-term molecular changes after AIE. HighlightsO_LIAdolescent intermittent ethanol (AIE) exposure decreased exploratory behavior in adult male and female mice. C_LIO_LIIn females, but not males, AIE increased anxiety-like behavior. C_LIO_LIIn males, but not females, AIE reduced stress reactivity in adulthood. C_LIO_LIThese findings indicate sex differences in the enduring effects of AIE on exploratory and affective behaviors. C_LIO_LICerebellar Grin2B mRNA levels were increased in adulthood in both male and female AIE-exposed mice. C_LIO_LIThese findings add to the small, but growing literature on behavioral AIE effects in mice, and establish cerebellar excitatory synaptic gene expression as an enduring effect of adolescent ethanol exposure. C_LI

neuroscience↗

bioRxiv2020

Adolescent intermittent ethanol exposure induces sex-dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice

With alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. Adolescents are also more prone to substance use disorder during adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long-lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence and in young adulthood. The present set of experiments were divided into four stages: (1) chronic intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using an intermittent vapor inhalation with repeated binge pattern ethanol exposure from postnatal day (PND) 28-42. Following this, mice underwent abstinence during late adolescence from PND 43-49 (Experiment 1) or PND 43-69 (Experiment 2). Beginning on PND 49-76 (Experiment 1) or PND 70-97 (Experiment 2), mice were assessed for intermittent voluntary ethanol consumption using a two-bottle drinking procedure over 28 days. Male mice that were exposed to ethanol during adolescence showed increased ethanol consumption during later adolescence (Experiment 1) and in emerging adulthood (Experiment 2), while the female mice showed decreased ethanol consumption. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These data highlight sex-dependent vulnerability to developing substance use disorders in adulthood. Significance StatementCurrently, it is vital to determine the sex-dependent impact of binge alcohol exposure during adolescence, given that until recently females have largely been ignored. Here we show that adolescent male mice that are exposed to binge ethanol during adolescence show long-term changes in behavior in adulthood. In contrast, female mice show a transient decrease in ethanol consumption in adulthood and decreased motor activity spent in the center zone of the open field test. Male mice appear to be more susceptible to the long-term changes in ethanol consumption following binge ethanol exposure during adolescence.

neuroscience↗

bioRxiv2019

Social interaction with an alcohol-intoxicated or cocaine-injected peer selectively alters social behaviors and drinking in adolescent male and female rats.

BackgroundDrinking alcohol is facilitated by social interactions with peers, especially during adolescence. The importance of peer social influences during adolescence on alcohol and substance use have recently received more attention. We have shown that social interaction with an alcohol-intoxicated peer influences adolescent alcohol drinking differently in male and female rats using the demonstrator-observer paradigm. The present set of experiments analyzed the social interaction session to determine behaviors that influence alcohol drinking in adolescent male and female rats.\n\nMethodsSpecifically, in experiment one we determined which behaviors were altered during social interaction with an alcohol-intoxicated demonstrator and assessed changes in ethanol intake in adolescent observers. Experiment two examined changes in voluntary saccharin consumption to determine if social interaction with an alcohol-intoxicated demonstrator altered consumption of a palatable solution. In experiment three, we administered a low (5 mg/kg) or high (20 mg/kg) dose of cocaine to the demonstrator and assessed changes in the adolescent observers to determine if social interaction with a drugged peer altered social behaviors and voluntary ethanol intake.\n\nResultsWe showed that social interaction with an alcohol-intoxicated demonstrator (1) decreased social play and increased social investigation and social contact in adolescent male and female observers, (2) did not alter non-social behaviors, (3) did not alter saccharin consumption and (4) increased voluntary ethanol intake in adolescent female but not male observers. When the peer was injected with cocaine (1) social play was dose-dependently decreased, (2) there were no changes in other social or non-social behaviors, and (3) voluntary ethanol intake in adolescent male and female observers was unaffected.\n\nConclusionsThe present results are consistent and extend our previous work showing that social interaction with an alcohol-intoxicated peer selectively alters social behaviors and alcohol-drinking in adolescent rats. Females appear to be more sensitive to elevating effects of social interaction on voluntary ethanol consumption.

animal behavior and cognition↗