Marta Rodríguez-Arias

• PhD
• Professor (Full) at University of Valencia

Extracellular vesicles derived from mesenchymal stromal cells (MSC-EVs) have emerged as a promising form of regenerative and immunomodulatory therapy; indeed, micro (mi)RNAs contained within MSC-EVs modulate target gene expression and impact disease-associated pathways. Chronic alcohol consumption results in neuroinflammation, brain damage, and imp...

Stress is a critical factor in the development of mental disorders such as addiction, underscoring the importance of stress resilience strategies. While the ketogenic diet (KD) has shown efficacy in reducing alcohol consumption in male mice without cognitive impairment, its impact on the stress response and addiction development, especially in fema...

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA targets to achieve these effects have no...

Stress is a critical factor in the development of mental disorders such as addiction, underscoring the importance of stress resilience strategies. While the ketogenic diet (KD) has shown efficacy in reducing alcohol consumption in male mice without cognitive impairment, its impact on the stress response and addiction development, especially in fema...

Background and Purpose New psychoactive substances such as N‐ethylpentylone (NEP) are continuously emerging in the illicit drug market, and knowledge of their effects and risks, which may vary between sexes, is scarce. Our present study compares some key effects of NEP in male and female mice. Experimental Approach Psychostimulant, rewarding and r...

Mice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show...

The endocannabinoid system is involved in multiple drug-related behavior as well as in the stress response. The transient increase in endogenous cannabinoids as well as endocannabinoid-like molecules contributes to healthy adaptation to stress exposure. In this study, we tested the effect of systemic OEA treatment (10mg/kg) before or after social d...

Oleoylethanolamide (OEA) is a lipid with anti-inflammatory activity that modulates multiple reward-related behaviors. Previous studies have shown that OEA treatment reduces alcohol self-administration (SA) while inhibiting alcohol-induced inflammatory signaling. Nevertheless, the specific mechanisms that OEA is targeting to achieve these effects ha...

Exposure to social defeat (SD) induces a depressive phenotype, increased ethanol seeking and consumption, accompanied by activation of the neuroinflammatory response. However, a resilient response can be potentiated through physical exercise in the form of voluntary wheel running (VWR) during or after exposure to social stress. Therefore, the aim o...

Background Extracellular vesicles (EVs) are heterogeneous membrane vesicles secreted by cells in extracellular spaces that play an important role in intercellular communication under both normal and pathological conditions. Mesenchymal stem cells (MSC) are anti‐inflammatory and immunoregulatory cells capable of secreting EVs, which are considered p...

Rationale Social stress contributes to the development of depressive and anxiety symptomatology and promotes pro-inflammatory signaling in the central nervous system. In this study, we explored the effects of a lipid messenger with anti-inflammatory properties – oleoylethanolamide (OEA) – on the behavioral deficits caused by social stress in both m...

The lipid oleoylethanolamide (OEA) has been shown to affect reward-related behavior. However, there is limited experimental evidence about the specific neurotransmission systems OEA may be affecting to exert this modulatory effect. The aim of this study was to evaluate the effects of OEA on the rewarding properties of cocaine and relapse-related ge...

Background Food addiction (FA) is characterised by symptoms such as loss of control over food consumption, inability to reduce consumption despite the desire to do so, and continued consumption despite negative consequences. The modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) is a widely used instrument to assess FA. Objectives To validate the...

Stress is a critical factor in the development of mood and drug use disorders. The social defeat model is not appropriate for female rodents due to their low level of aggression. Therefore, a robust female model of social stress needs to be developed and validated. The aim of the present study was to unravel the long-lasting effects of vicarious so...

The lipid-derived messenger oleoylethanolamide (OEA) has been involved in multiple physiological functions including metabolism and the immune response. More recently, OEA has been observed to affect reward-related behavior. Stress is a major risk factor for drug use and a predictor of drug relapse. In the laboratory, social stress has been largely...

The present paper evaluates the effect of physical activity on the increase of the conditioned rewarding effects of cocaine induced by intermittent social stress and on the neuroinflammatory response that contributes to the enhancement of drug response. For that purpose, three studies were designed in which social stress was induced in different sa...

Background COVID-19 confinement affected lifestyles. There is inconclusive evidence about changes in eating patterns, and there are few studies on the impact on body mass index (BMI), the occurrence of dysfunctional behaviors (binge eating, fat intake), and the predictive role of maladaptive eating styles (emotional, external, and restrained eating...

Empathy deficits have been proposed to be an important factor for intimate partner violence (IPV). IPV perpetrators have shown a differential change in salivary oxytocin (sOXT), testosterone (sT), and cortisol (sC), following empathic and stress tasks, compared to non-violent men. However, the influence of empathic deficits in those hormones after...

Adverse social experiences during adolescence are associated with the appearance of mental illness in adulthood. Social defeat (SD) is an ethologically valid murine model to study the consequences of social stress. In adolescent mice, SD induces depressive-like behaviors, increased anxiety and potentiates the reinforcing effects of cocaine and alco...

In recent years, nutritional interventions for different psychiatric diseases have gained increasing attention, such as the ketogenic diet (KD). This has led to positive effects in neurological disorders such as Parkinson's disease, addiction, autism or epilepsy. The neurobiological mechanisms through which these effects are induced and the effects...

In recent years, the benefits of the ketogenic diet (KD) on different psychiatric disorders have been gaining attention, but the substance abuse field is still unexplored. Some studies have reported that palatable food can modulate the rewarding effects of cocaine, but the negative metabolic consequences rule out the recommendation of using it as a...

N-ethyl-pentedrone (NEPD, 2-(ethylamino)-1-phenyl-1-pentanone) is one of the latest synthetic cathinone derivatives that emerged into the illicit drug market. This drug has psychostimulant properties and has been related with several intoxications and even fatalities. However, information about the consequences of its acute and repeated consumption...

Intimate partner violence (IPV) has been linked to difficulties in socio-affective functions. Nevertheless, the underlying psychobiological mechanisms that might be responsible for them remain unclear. Oxytocin (OXT) stands out as an important hormone that may favor the salience of social information, due to its relevance in empathy and prosocial b...

Neurogenesis in the adult brain takes place in two neurogenic niches: the ventricular-subventricular zone (V-SVZ) and the subgranular zone. After differentiation, neural precursor cells (neuroblasts) have to move to an adequate position, a process known as neuronal migration. Some studies show that in Alzheimer’s disease, the adult neurogenesis is...

N‐ethyl‐pentylone (NEP), also known as ‘ephylone’ and N‐ethylnorpentylone, has been identified as one of the most recent novel psychostimulants to emerge into the illicit drug market and it has been associated with some intoxications and even fatalities. However, little is known about the consequences of its repeated consumption as well as the role...

Large preclinical evidence shows that exposure to social defeat (SD) increases vulnerability to drug abuse, increasing the consumption of ethanol. However, not all subjects are equally affected by the changes induced by stress. Previous reports have evidenced that the resilient phenotype to depressive-like behaviors after SD is associated with the...

The immune system provides the first line of the organism's defenses, working to maintain homeostasis against external threats and respond also to internal danger signals. There is much evidence to suggest that modifications of inflammatory parameters are related to vulnerability to develop mental illnesses, such as depression, autism, schizophreni...

The kynurenine (KYN) pathway of tryptophan (TRP) degradation is activated by stress and inflammatory factors. It is now well established that social stress induces the activation of the immune system, with central inflammation and KYN metabolism being two of the main factors linking stress with depression. The aim of the present study was to evalua...

Many of the various factors, characteristics, and variables involved in the addictive process can determine an individual's vulnerability to develop drug addiction. Hedonic eating, based on pleasure rather than energy needs, modulates the same reward circuits, as do drugs of abuse. According to the last report of the World Health Organization, the...

Rationale Palatable food and drugs of abuse activate common neurobiological pathways and numerous studies suggest that fat consumption increases vulnerability to drug abuse. In addition, preclinical reports show that palatable food may relieve craving for drugs, showing that an ad libitum access to a high-fat diet (HFD) can reduce cocaine-induced r...

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body’s metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to st...

Stress is one of the main risk factors that can induce humans to develop disorders such as depression, anxiety, or drug use. One of the main sources of stress is social interaction, which can lead to situations such as bullying at school or at work. In this article we will review the close relationship between exposure to stressful situations and i...

Background: Only a few studies have paid attention to the ability of perpetrators of intimate partner violence (IPVAW) against women to cope with acute stress, including hormonal parameters. In fact, previous studies assessed how salivary testosterone (Tsal) and cortisol (Csal) changed after coping with an acute emotional stressor (directly relate...

Alcohol binge drinking (BD) and poor nutritional habits are two frequent behaviors among many adolescents that alter gut microbiota in a pro-inflammatory direction. Dysbiotic changes in the gut microbiome are observed after alcohol and high-fat diet (HFD) consumption, even before obesity onset. In this study, we investigate the neuroinflammatory re...

Using the social defeat (SD) model, numerous studies have shown that stressed mice display an enhanced response to the motivational effects of cocaine in the self-administration (SA) and conditioned-place preference (CPP) paradigms. However, not all subjects exposed to stress express its harmful effects. Some are particularly susceptible to the del...

Alzheimer's disease (AD), the most prevalent form of dementia, remains incurable mainly due to our failings in the search for effective pharmacological strategies. Here, we describe the development of targeted multimodal polypeptide-based nanoconjugates as potential AD treatments. Treatment with polypeptide nanoconjugates bearing propargylamine moi...

There is huge scientific interest in the neuropeptide oxytocin (OXT) due to its putative capacity to modulate a wide spectrum of physiological and cognitive processes including motivation, learning, emotion, and the stress response. The present review seeks to increase the understanding of the role of OXT in an individual’s vulnerability or resilie...

Background Substance use disorders and social stress are currently associated with changes in the immune system response by which they induce a proinflammatory state in neurons and glial cells that eventually modulates the reward system. Aims The aim of the present work was to assess the role of the immune TLR4 (Toll-like receptors 4) and its sign...

Oxytocin (OXT) modulates social interactions, attenuates stressful responses and can decrease drug-seeking and taking behaviors. In previous studies, we observed that social defeat (SD) induced a long-lasting increase in ethanol intake and neuroinflammation in male mice. We also know that OXT blocks the increase in cocaine reward induced by SD. The...

Background: Binge drinking is an important health problem, and it has been related to binge eating and fat intake in animal models, but this relationship has not been tested in humans. The first objective of this study was to analyze whether binge eating and fat intake are related to binge drinking in a youth sample. The second objective was to an...

The aim of this study was to evaluate the effects of cannabidiol (CBD) on the behavioural and gene expression changes in a new animal model of spontaneous cocaine withdrawal. For this purpose, male CD-1 mice were exposed to progressive increasing doses of cocaine for 12 days (15 to 60 mg/kg/day, i.p.), evaluating spontaneous cocaine withdrawal 6 h...

Adolescence is a brain maturation developmental period during which remodeling and changes in synaptic plasticity and neural connectivity take place in some brain regions. Different mechanism participates in adolescent brain maturation, including autophagy that plays a role in synaptic development and plasticity. Alcohol is a neurotoxic compound an...

Foods that are rich in fats ans sugars are pleasurable because they stimulate our reward circuits, the same ones that are activated by drugs. In a context in which unhealthy diets and drug abuse are common from adolescence, it is important to investigate its consequences. This article reviews the relationship between especially tasty food, our brai...

Alcohol interferes with foetal development and prenatal alcohol exposure can lead to adverse effects known as foetal alcohol spectrum disorders. We aimed to assess the underlying neurobiological mechanisms involved in alcohol intake and withdrawal in adolescent mice exposed to alcohol during early life stages, in discrete brain areas. Pregnant C57B...

Objectives: Mindfulness and compassion-based interventions (MCBI) have shown to be effective in increasing self-reported empathy in healthcare professionals. However, no studies described a beneficial effect of MCBI on biological variables related to empathy. In this study, we analyze the effects of an MCBI on the basal levels of salivary oxytocin...

Social factors have a dual influence on addictive disorders. While social defeat stress in rodents increases the response to drug reward, positive social conditions, such as pair housing, increase stress resilience. The objective of the present study was to confirm whether oxytocin (OT) mediates this social buffering. To this end, male mice were ho...

Previous studies have shown that exposure to social defeat (SD), a model of social stress, produces a long-term increase in the consumption of ethanol, most likely through an increase in the neuroinflammation response. The aim of the present study was to evaluate whether exposure to physical activity in the form of voluntary wheel running (VWR) cou...

Mindfulness‐based interventions (MBI) have been shown to be effective in increasing empathy in health professionals. Yet, more research is needed to analyze the specific influence of mindfulness exercises on biological variables involved in empathy, such as the biological system of oxytocin activity. In this study, we analyze the effects of a brief...

Unhealthy diet and alcohol are serious health problems, especially in adolescents and young adults. “Binge” is defined as the excessive and uncontrolled consumption of food (binge eating) and alcohol (binge drinking). Both behaviors are frequent among young people and have a highly negative impact on their health and quality of life. Several studie...

Preclinical studies have shown that social stress increases vulnerability to the reinforcing effects of cocaine. However, the results are not always homogeneous, revealing a subpopulation that does not show a preference for cocaine. Thus, the main aim of the present study was to characterize the behavioral profile of resilient mice to the stress-in...

Eating is necessary for survival, but it is also one of the great pleasures enjoyed by human beings. Research to date shows that palatable food can be rewarding in a similar way to drugs of abuse, indicating a considerable comorbidity between eating disorders and substance-use disorders. Analysis of the common characteristics of both types of disor...

Previous research in rodents suggests that the long-term neurobehavioral disturbances induced by chronic ethanol (EtOH) exposure could be due to endocannabinoid system (ECS) alterations. Moreover, ECS failure has been proposed to mediate the cognitive impairment and β-amyloid production in Alzheimer disease (AD). Thus, in the present study, we eval...

Glutamate excitotoxicity has long been related to Alzheimer’s disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double tra...

Background: Dietary factors have significant effects on the brain, modulating mood, anxiety, motivation and cognition. To date, no attention has been paid to the consequences that the combination of ethanol (EtOH) and a high-fat diet (HFD) have on learning and mood disorders during adolescence. The aim of the present work was to evaluate the bioch...

Rationale Previous studies have demonstrated that repeated social defeat (RSD) stress only induces cognitive deficits when experienced during adulthood. However, RSD increases cocaine-rewarding effects in adult and adolescent mice, inducing different expressions of proBDNF in the ventral tegmental area. Objective The aim of the present study was t...

Social stress is associated with higher vulnerability to drug use, as it enhances the reinforcing effects of psychostimulants in rodents. Furthermore, continued or severe stress induces a proinflammatory state of microglial activation and augmented cytokine production. The aim of the present work was to evaluate the role of fractalkine [C-X3-C moti...

Social defeat is considered the most representative animal model for studying the consequences of social stress. Intermittent social defeat (ISD) has proved to enhance the response to cocaine hedonic properties. In the present research, we evaluated if different social housing conditions, as housing with a familiar conspecific or with a female, exe...

Over the past few years, the effects of a high-fat diet (HFD) on cognitive functions have been broadly studied as a model of obesity, although no studies have evaluated whether these effects are maintained after the cessation of this diet. In addition, the behavioral effects of having a limited access to an HFD (binge-eating pattern) are mostly unk...

Introduction: The Binge Eating Scale (BES) is a widely used self-report questionnaire to identify compulsive eaters. However, research on the dimensions and psychometric properties of the BES is limited. Objective: The aim of this study was to examine the properties of the Spanish version of the BES. Methods: Confirmatory Factor Analyses (CFAs) wer...

[This corrects the article DOI: 10.1371/journal.pone.0209291.].

It is well established that repeated social defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were d...

IL-6 concentration data. (XLSX)

EPM experimental data. (XLSX)

CPP experimental data. (XLSX)

Psychiatric eating disorders (ED) and substance use disorder (SUD) are frequent comorbidities and negatively affect evaluation, treatment, and prognosis of both pathologies. The aim of the present study was to determine the prevalence of eating disorders amongst patients seeking treatment for SUD, mainly alcohol, cocaine, and cannabis, and the modu...

The neuropeptide oxytocin (OXT) plays a critical role in the regulation of social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated social defeat (RSD). During the social defeat...

The experience of social stress during adolescence is associated with higher vulnerability to drug use. Increases in the acquisition of cocaine self-administration, in the escalation of cocaine-seeking behavior, and in the conditioned rewarding effects of cocaine have been observed in rodents exposed to repeated social defeat (RSD). In addition, pr...

Experimental data. (XLSX)

Many vegetable extracts, essential oils, and their main constituents are active on the Central Nervous System (CNS). In fact, they have been used as sedatives, hypnotics, or tranquilizers for their activity in treating CNS disorders. In this research, we studied the possible activities of Lavandula angustifolia (LA) essential oil and of its main co...

Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to social defeat experiences (brief episodes of social confrontations during adolescence and adulthood), the rodent brain undergo...

Addiction pharmacotherapy aims to prevent drug abstinence symptoms, reduce drug craving and relapse, and normalize physiologic functions disrupted by chronic use of the drug. During the last 50 years, there has been an enormous revolution in pharmacotherapy for drug addiction. From abstinence as practically the only treatment option available, ther...

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to acquire a conditioned place preference in a drug-paired compartment, and after the post-conditioning test, they perform several sessions to extinguish the established preference. The CPP permits...

There is a marked comorbidity between alcohol abuse and eating disorders, especially in the young population. We have previously reported that bingeing on fat during adolescence increases the rewarding effects of ethanol (EtOH). The aim of the present work was to study if vulnerability to EtOH persists after cessation of binge eating. OF1 mice bing...

Training and saccharin substitution phases. (XLSX)

Numerous studies have shown that social defeat stress induces an increase in the rewarding effects of cocaine. In this study we have investigated the role played by the main hypothalamic stress hormone, corticotropin-releasing factor (CRF), in the effects that repeated social defeat (RSD) induces in the conditioned rewarding effects and locomotor s...

Binge eating is a specific form of overeating characterized by intermittent, excessive eating. To date, several studies have addressed the effects that bingeing on fat has on the rewarding effects of drugs of abuse, but they have found contradictory and highly variable results. Housing conditions could modulate these results, as most studies employ...

RationalePreclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants. Objectives The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC)...

Background Inflammation during brain development participates in the pathogenesis of early brain injury and cognitive dysfunctions. Prenatal ethanol exposure affects the developing brain and causes neural impairment, cognitive and behavioral effects, collectively known as fetal alcohol spectrum disorders (FASD). Our previous studies demonstrate tha...

RationaleRepeated social defeat (RSD) increases the rewarding effects of cocaine in adolescent and adult rodents. Objective The aim of the present study was to compare the long-term effects of RSD on the conditioned rewarding effects of cocaine and levels of the transcription factors Pitx3 and Nurr1 in the ventral tegmental area (VTA), the dopamine...

Psychiatric disorders constitute one of the main causes of disability worldwide. During the past years, considerable research has been conducted on the genetic architecture of such diseases, although little understanding of their etiology has been achieved. The difficulty to access up-to-date, relevant genotype-phenotype information has hampered th...

Chronic cannabinoid consumption is an increasingly common behavior among teenagers and has been shown to cause long-lasting neurobehavioral alterations. Besides, it has been demonstrated that cocaine addiction in adulthood is highly correlated with cannabis abuse during adolescence. Cocaine consumption and subsequent abstinence from it can cause ps...

It is estimated that 2.1 million young adults used MDMA/Ecstasy in the last year in Europe. Vulnerable subjects can develop dependence after MDMA abuse but currently there does not exist an effective treatment for this disorder. The nitric oxide (NO) pathway seems to have an important role on the rewarding effects of different drugs and has been pr...

Binge-eating is considered a specific form of overeating characterized by intermittent and high caloric food intake in a short period of time. Epidemiologic studies support a positive relation between the ingestion of fat and ethanol (EtOH), specifically among adolescent subjects. The aim of this work was to clarify the role of the compulsive, limi...