Víctor Echeverry - Profile on Academia.edu (original) (raw)

Papers by Víctor Echeverry

Face and Predictive Validities of a Preclinical Model of Operant Binge Drinking

HAL (Le Centre pour la Communication Scientifique Directe), 2019

Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Addiction Biology

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ay... more Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5‐HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group ...

Review The genetic basis of the endocannabinoid system and drug addiction in humans

The cannabinoid receptor (CNR1) and the fatty acid amide hydrolase (FAAH) genes are located on ch... more The cannabinoid receptor (CNR1) and the fatty acid amide hydrolase (FAAH) genes are located on chromosomes 6 and 1 in the 6q15 and 1p33 cytogenetic bands, respectively. CNR1 encodes a seven-transmembrane domain protein of 472 amino acids, whereas FAAH encodes one transmembrane domain of 579 amino acids. Several mutations found in these genes lead to altered mRNA stability and transcription rate or a reduction of the activity of the encoded protein. Increasing evidence shows that these functional mutations are related to dependence upon cocaine, alcohol, marijuana, heroin, nicotine and other drugs. One of the most compelling associations is with the C385A single nucleotide polymorphism (SNP), which is found in the FAAH gene. For all of the genetic polymorphisms reviewed here, it is difficult to form overall conclusions due to the high diversity of population samples being studied, ethnicity, the use of volunteers, heterogeneity of the recruitment criteria and the drug addiction pheno...

Psychopharmacology, 2020

Rationale Since energy drinks (EDs) were marketed to the general public as recreational and soft ... more Rationale Since energy drinks (EDs) were marketed to the general public as recreational and soft drinks, mixing these with alcohol has become a popular practice, especially in the younger population. Alcohol mixed with EDs (AmEDs) is a particularly alarming combination, given the evidence that consistently associate these drinks with increased risk behaviours and greater alcohol consumption. Caffeine and taurine are commonly found in EDs. In contrast to caffeine, the studies on taurine psychoactive properties and how this amino acid influences ethanol intake alone or in combination with caffeine are not so numerous. Objectives We summarised relevant and available data on the studies focusing on taurine as a psychoactive agent and its influence on ethanol (EtOH)-induced behaviours. Given the increased risk that represents mixing alcohol with energy drinks, we put emphasis on the research exploring the impact of these combinations on motivated behaviour towards EtOH consumption. Results The research on taurine properties on motivated behaviour towards EtOH consumption is limited, and mostly all done in combination with caffeine or other molecules. This makes it difficult to elucidate the effect of this amino acid when combined with alcohol. Conclusions Incomplete understanding of the properties and effects of AmEDs is unavoidable until more studies are performed on the influence of taurine on motivation to consume alcohol. Taurine should be further explored, particularly in regard to its potential beneficial applications, motivational properties and synergies with other psychoactive ingredients (i.e. caffeine).

Cocaine reverses the naltrexone-induced reduction in operant ethanol self-administration: The effects on immediate-early gene expression in the rat prefrontal cortex

Neuropharmacology, 2012

Naltrexone is a clinically approved medication for alcoholism. We aimed to investigate the effect... more Naltrexone is a clinically approved medication for alcoholism. We aimed to investigate the effectiveness of naltrexone co-administered with cocaine and the association of these substances with immediate-early gene expression in the rat prefrontal cortex. We used chronic operant ethanol self-administration and oral treatments prescribed for alcoholism and available in pharmacies to maximise the predictive validity in humans. We performed real-time PCR analysis to determine gene expression levels in the prefrontal cortex. Only the highest dose of naltrexone (1, 3, and 10 mg/kg, p.o.) reduced the response to ethanol. Cocaine increased ethanol self-administration in a dose-dependent manner (2.5, 10, 20 mg/kg, i.p.) and reversed the naltrexone-induced reduction. Naltrexone failed to prevent the cocaine-induced increase in locomotor activity observed in these animals. Chronic self-administration of ethanol reduced the expression of the C-fos gene 4- to 12-fold and increased expression of the COX-2 (up to 4-fold) and Homer1a genes in the rat prefrontal cortex. Chronic ethanol self-administration is prevented by naltrexone, but cocaine fully reverses this effect. This result suggests that cocaine may overcome naltrexone's effectiveness as a treatment for alcoholism. The ethanol-induced reduction in C-fos gene expression in the prefrontal cortex reveals an abnormal activity of these neurons, which may be relevant in the compulsive consumption of ethanol, the control of reward-related areas and the behavioural phenotype of ethanol addiction.

Dissecting operant alcohol self‐administration using saccharin‐fading procedure

Neuropsychopharmacology Reports

Seroprevalence of anti-SARS-CoV-2 IgG antibodies: relationship with COVID-19 diagnosis, symptoms, smoking, and method of transmission

IJID Regions

El consumo de sustancias psicoactivas, y en concreto el consumo simultaneo de alcohol y cocaina, ... more El consumo de sustancias psicoactivas, y en concreto el consumo simultaneo de alcohol y cocaina, es una practica frecuente en la poblacion general. Asi mismo, se ha visto que el consumo de cocaina incrementa el riesgo de desarrollar dependencia de alcohol, y viceversa. Actualmente existen 4 tratamientos farmacologicos aprobados para la dependencia de alcohol, siendo el disulfiram el primer tratamiento aprobado, posteriormente lo fueron la naltrexona y el acamprosato, y recientemente el nalmefeno. Por otra parte, estudios clinicos recientes han senalado que el topiramato, un farmaco aprobado para el tratamiento de la epilepsia y la prevencion de la migrana, podria ser efectivo para el tratamiento de la dependencia de alcohol o cocaina. Sin embargo, para esta ultima no existe aun ninguna terapia farmacologica aprobada, y se conoce muy poco acerca de la eficacia de estas farmacoterapias en la codependencia de alcohol y cocaina...

Psicothema, 2019

BACKGROUND Experimental substance use among young people is related to individual factors includi... more BACKGROUND Experimental substance use among young people is related to individual factors including personality traits such as impulsivity and sensation seeking, and genetic variations such as single nucleotide polymorphisms (SNPs) in the fatty acid amide hydrolase (FAAH) gene. The objective of this study is to analyze the relationship between these three sets of variables. METHODS Volunteer undergraduate students (N = 861, 76% female, M = 20.7 years) completed an ad hoc questionnaire on variables related to their consumption of alcohol, tobacco, cannabis, synthetic drugs and cocaine. In addition, 591 of them completed the Barratt Impulsiveness Scale-11 (BIS-11) and the Sensation Seeking Scale-V (SSS-V). All participants were genotyped in FAAH C385A SNP and its proxy variant rs12075550. RESULTS Consistent with previous data, both impulsivity and sensation seeking were associated with most of the variables related to experimental substance use. In addition, we found the first evidenc...

International Journal of Molecular Sciences, 2021

The human gut is the largest organ with immune function in our body, responsible for regulating t... more The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted muco...

Autism Research, 2021

Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in th... more Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in the etiopathology of autism spectrum disorder (ASD). Previous mouse studies have investigated the role of ECS in several behavioral domains; however, none of them has performed an extensive assessment of social and communication behaviors, that is, the main core features of ASD. This study employed a mouse line lacking the primary endocannabinoid receptor (CB1r) and characterized ultrasonic communication and social interaction in CB1−/−, CB1+/−, and CB1+/+ males and females. Quantitative and qualitative alterations in ultrasonic vocalizations (USVs) were observed in CB1 null mice both during early development (i.e., between postnatal days 4 and 10), and at adulthood (i.e., at 3 months of age). Adult mutants also showed marked deficits in social interest in the three‐chamber test and social investigation in the direct social interaction test. These behavioral alterations were mostly observe...

French Journal of Psychiatry, 2018

Alcoholism: Clinical and Experimental Research, 2020

Background: Pleiotrophin (PTN) and Midkine (MK) are cytokines that are upregulated in the prefron... more Background: Pleiotrophin (PTN) and Midkine (MK) are cytokines that are upregulated in the prefrontal cortex (PFC) after alcohol administration and have been shown to reduce alcohol intake and reward. Both cytokines are endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1). Recently, a new compound named MY10 was designed with the aim of mimicking the activity of PTN and MK. MY10 has already shown promising results regulating alcohol-related behaviors in mice. Methods: We have now tested the effects of MY10 on alcohol operant self-administration and Drinking In the Dark-Multiple Scheduled Access (DID-MSA) paradigms in rats. Gene expression of relevant genes in the PTN/MK signalling pathway in the PFC was analyzed by real-time PCR. Results: MY10, at the highest dose tested (100 mg•kg -1 ), reduced alcohol consumption in the alcohol operant self-administration paradigm (p=0.040). In the DID-MSA paradigm, rats drank significantly less alcohol (p=0.019) and showed a significant decrease in alcohol preference (p=0.002). We observed that the longer the exposure to alcohol, the greater the suppressing effects of MY10 on alcohol consumption. It was demonstrated that the effects of MY10 were specific to alcohol since saccharin intake was not affected by MY10 (p=0.804). MY10 prevented the alcoholinduced downregulation of Ptprz1 (p=0.004) and Anaplastic Lymphoma kinase (Alk) (p=0.013) expression. Our results support and provide further evidence regarding the efficacy of MY10 on alcohol-related behaviors and suggest the consideration of the blockade of RPTPβ/ζ as a target for reducing excessive alcohol consumption.

Is R(+)‐Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side

Addiction Biology, 2020

For several decades, studies conducted to evaluate the efficacy of RS(±)‐Baclofen in the treatmen... more For several decades, studies conducted to evaluate the efficacy of RS(±)‐Baclofen in the treatment of alcohol dependence yielded contrasting results. Human and animal studies recently questioned the use of the racemic drug in patients since a potential important role of the different enantiomers has been revealed with an efficacy thought to reside with the active R(+)‐enantiomer. Here we conducted experiments in the postdependent rat model of alcohol dependence to compare the efficacy of R(+)‐Baclofen or S(−)‐Baclofen to that of RS(±)‐Baclofen on ethanol intake, seeking, and relapse. R(+)‐Baclofen was more effective than RS(±)‐Baclofen in reducing ethanol intake and seeking during acute withdrawal and during relapse after abstinence. We also used an original population approach in order to identify drug responders. We found a significant proportion of responders to S(−)‐Baclofen and RS(±)‐Baclofen, displaying an increase in ethanol intake, and this increasing effect on alcohol intak...

Nutrients, 2018

Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been asso... more Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA’s beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE−/−) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased Aβ, ß-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concen...

Behavioural Brain Research, 2019

Although the genetic influence on global stopping has been extensively investigated, little is kn... more Although the genetic influence on global stopping has been extensively investigated, little is known about the genetic contribution to other more complex forms of inhibitory control such as selective stopping. The selectivity of inhibitory control can be assessed by using the stimulus-selective stop-signal task. Notably, recent behavioural and neural evidence indicates that individuals can adopt selective but also non-selective stopping strategies to solve it. This study aimed to investigate for the first time the influence of two relevant dopaminergic polymorphisms (in COMT and DRD2 genes) on stimulus-selective stopping in a sample of 529 adults. Results showed that although none of these polymorphisms (neither individually nor in combination) modulate the latency of the stop process in each strategy (the stop-signal reaction time), the choice of strategy was influenced by their interaction. These results suggest that dopaminergic polymorphisms might influence strategy adoption in selective stopping paradigms, which constitutes a novel finding.

Addiction Biology, 2018

Binge drinking (BD) is often defined as a large amount of alcohol consumed in a ‘short’ period of... more Binge drinking (BD) is often defined as a large amount of alcohol consumed in a ‘short’ period of time or ‘per occasion’. In clinical research, few researchers have included the notion of ‘speed of drinking’ in the definition of BD. Here, we aimed to describe a novel pre‐clinical model based on voluntary operant BD, which included both the quantity of alcohol and the rapidity of consumption. In adult Long–Evans male rats, we induced BD by regularly decreasing the duration of ethanol self‐administration from 1‐hour to 15‐minute sessions. We compared the behavioral consequences of BD with the behaviors of rats subjected to moderate drinking or heavy drinking (HD). We found that, despite high ethanol consumption levels (1.2 g/kg/15 minutes), the total amounts consumed were insufficient to differentiate HD from BD. However, consumption speed could distinguish between these groups. The motivation to consume was higher in BD than in HD rats. After BD, we observed alterations in locomotor ...

Addiction Biology, 2017

Mixing alcohol with caffeinated energy drinks is a common practice, especially among young people... more Mixing alcohol with caffeinated energy drinks is a common practice, especially among young people. In humans, the research on this issue has mainly focused on the use of the mass‐marketed energy drinks themselves, whereas in animal models, it has focused on the individual effects of their active ingredients (i.e. caffeine). Here, we have characterized how Red Bull®, one of the most consumed caffeinated energy drink worldwide, modulates operant alcohol self‐administration in Wistar rats. We found that animals readily and steadily responded for Red Bull (mean: 90 responses, 30 minutes and fixed‐ratio 1), which was accompanied by locomotor stimulating effects (26 percent increase). The higher the concentration of alcohol (3–20 percent), the higher the consumption of alcohol (g/kg) and associated blood alcohol levels (91.76 percent) in the mixed Red Bull–alcohol group (60 percent increase). Blood caffeine levels in the Red Bull group were 4.69 μg/ml and 1.31 μg/ml in the Red Bull–alcoho...

Stem Cells, 2016

The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracell... more The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracellular levels of cyclic adenosine 3′,5′-monophosphate in the immune and central nervous system. We have previously shown that inhibitors of this enzyme are potent neuroprotective and anti-inflammatory agents. In addition, we also demonstrated that PDE7 inhibition induces endogenous neuroregenerative processes toward a dopaminergic phenotype. Here, we show that PDE7 inhibition controls stem cell expansion in the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the subventricular zone (SVZ) in the adult rat brain. Neurospheres cultures obtained from SGZ and SVZ of adult rats treated with PDE7 inhibitors presented an increased proliferation and neuronal differentiation compared to control cultures. PDE7 inhibitors treatment of neurospheres cultures also resulted in an increase of the levels of phosphorylated cAMP response element binding protein, suggesting that their effect...

Face and Predictive Validities of a Preclinical Model of Operant Binge Drinking

HAL (Le Centre pour la Communication Scientifique Directe), 2019

Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies

Addiction Biology

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ay... more Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5‐HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group ...

Review The genetic basis of the endocannabinoid system and drug addiction in humans

The cannabinoid receptor (CNR1) and the fatty acid amide hydrolase (FAAH) genes are located on ch... more The cannabinoid receptor (CNR1) and the fatty acid amide hydrolase (FAAH) genes are located on chromosomes 6 and 1 in the 6q15 and 1p33 cytogenetic bands, respectively. CNR1 encodes a seven-transmembrane domain protein of 472 amino acids, whereas FAAH encodes one transmembrane domain of 579 amino acids. Several mutations found in these genes lead to altered mRNA stability and transcription rate or a reduction of the activity of the encoded protein. Increasing evidence shows that these functional mutations are related to dependence upon cocaine, alcohol, marijuana, heroin, nicotine and other drugs. One of the most compelling associations is with the C385A single nucleotide polymorphism (SNP), which is found in the FAAH gene. For all of the genetic polymorphisms reviewed here, it is difficult to form overall conclusions due to the high diversity of population samples being studied, ethnicity, the use of volunteers, heterogeneity of the recruitment criteria and the drug addiction pheno...

Psychopharmacology, 2020

Rationale Since energy drinks (EDs) were marketed to the general public as recreational and soft ... more Rationale Since energy drinks (EDs) were marketed to the general public as recreational and soft drinks, mixing these with alcohol has become a popular practice, especially in the younger population. Alcohol mixed with EDs (AmEDs) is a particularly alarming combination, given the evidence that consistently associate these drinks with increased risk behaviours and greater alcohol consumption. Caffeine and taurine are commonly found in EDs. In contrast to caffeine, the studies on taurine psychoactive properties and how this amino acid influences ethanol intake alone or in combination with caffeine are not so numerous. Objectives We summarised relevant and available data on the studies focusing on taurine as a psychoactive agent and its influence on ethanol (EtOH)-induced behaviours. Given the increased risk that represents mixing alcohol with energy drinks, we put emphasis on the research exploring the impact of these combinations on motivated behaviour towards EtOH consumption. Results The research on taurine properties on motivated behaviour towards EtOH consumption is limited, and mostly all done in combination with caffeine or other molecules. This makes it difficult to elucidate the effect of this amino acid when combined with alcohol. Conclusions Incomplete understanding of the properties and effects of AmEDs is unavoidable until more studies are performed on the influence of taurine on motivation to consume alcohol. Taurine should be further explored, particularly in regard to its potential beneficial applications, motivational properties and synergies with other psychoactive ingredients (i.e. caffeine).

Cocaine reverses the naltrexone-induced reduction in operant ethanol self-administration: The effects on immediate-early gene expression in the rat prefrontal cortex

Neuropharmacology, 2012

Naltrexone is a clinically approved medication for alcoholism. We aimed to investigate the effect... more Naltrexone is a clinically approved medication for alcoholism. We aimed to investigate the effectiveness of naltrexone co-administered with cocaine and the association of these substances with immediate-early gene expression in the rat prefrontal cortex. We used chronic operant ethanol self-administration and oral treatments prescribed for alcoholism and available in pharmacies to maximise the predictive validity in humans. We performed real-time PCR analysis to determine gene expression levels in the prefrontal cortex. Only the highest dose of naltrexone (1, 3, and 10 mg/kg, p.o.) reduced the response to ethanol. Cocaine increased ethanol self-administration in a dose-dependent manner (2.5, 10, 20 mg/kg, i.p.) and reversed the naltrexone-induced reduction. Naltrexone failed to prevent the cocaine-induced increase in locomotor activity observed in these animals. Chronic self-administration of ethanol reduced the expression of the C-fos gene 4- to 12-fold and increased expression of the COX-2 (up to 4-fold) and Homer1a genes in the rat prefrontal cortex. Chronic ethanol self-administration is prevented by naltrexone, but cocaine fully reverses this effect. This result suggests that cocaine may overcome naltrexone's effectiveness as a treatment for alcoholism. The ethanol-induced reduction in C-fos gene expression in the prefrontal cortex reveals an abnormal activity of these neurons, which may be relevant in the compulsive consumption of ethanol, the control of reward-related areas and the behavioural phenotype of ethanol addiction.

Dissecting operant alcohol self‐administration using saccharin‐fading procedure

Neuropsychopharmacology Reports

Seroprevalence of anti-SARS-CoV-2 IgG antibodies: relationship with COVID-19 diagnosis, symptoms, smoking, and method of transmission

IJID Regions

El consumo de sustancias psicoactivas, y en concreto el consumo simultaneo de alcohol y cocaina, ... more El consumo de sustancias psicoactivas, y en concreto el consumo simultaneo de alcohol y cocaina, es una practica frecuente en la poblacion general. Asi mismo, se ha visto que el consumo de cocaina incrementa el riesgo de desarrollar dependencia de alcohol, y viceversa. Actualmente existen 4 tratamientos farmacologicos aprobados para la dependencia de alcohol, siendo el disulfiram el primer tratamiento aprobado, posteriormente lo fueron la naltrexona y el acamprosato, y recientemente el nalmefeno. Por otra parte, estudios clinicos recientes han senalado que el topiramato, un farmaco aprobado para el tratamiento de la epilepsia y la prevencion de la migrana, podria ser efectivo para el tratamiento de la dependencia de alcohol o cocaina. Sin embargo, para esta ultima no existe aun ninguna terapia farmacologica aprobada, y se conoce muy poco acerca de la eficacia de estas farmacoterapias en la codependencia de alcohol y cocaina...

Psicothema, 2019

BACKGROUND Experimental substance use among young people is related to individual factors includi... more BACKGROUND Experimental substance use among young people is related to individual factors including personality traits such as impulsivity and sensation seeking, and genetic variations such as single nucleotide polymorphisms (SNPs) in the fatty acid amide hydrolase (FAAH) gene. The objective of this study is to analyze the relationship between these three sets of variables. METHODS Volunteer undergraduate students (N = 861, 76% female, M = 20.7 years) completed an ad hoc questionnaire on variables related to their consumption of alcohol, tobacco, cannabis, synthetic drugs and cocaine. In addition, 591 of them completed the Barratt Impulsiveness Scale-11 (BIS-11) and the Sensation Seeking Scale-V (SSS-V). All participants were genotyped in FAAH C385A SNP and its proxy variant rs12075550. RESULTS Consistent with previous data, both impulsivity and sensation seeking were associated with most of the variables related to experimental substance use. In addition, we found the first evidenc...

International Journal of Molecular Sciences, 2021

The human gut is the largest organ with immune function in our body, responsible for regulating t... more The human gut is the largest organ with immune function in our body, responsible for regulating the homeostasis of the intestinal barrier. A diverse, complex and dynamic population of microorganisms, called microbiota, which exert a significant impact on the host during homeostasis and disease, supports this role. In fact, intestinal bacteria maintain immune and metabolic homeostasis, protecting our organism against pathogens. The development of numerous inflammatory disorders and infections has been linked to altered gut bacterial composition or dysbiosis. Multiple factors contribute to the establishment of the human gut microbiota. For instance, diet is considered as one of the many drivers in shaping the gut microbiota across the lifetime. By contrast, alcohol is one of the many factors that disrupt the proper functioning of the gut, leading to a disruption of the intestinal barrier integrity that increases the permeability of the mucosa, with the final result of a disrupted muco...

Autism Research, 2021

Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in th... more Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in the etiopathology of autism spectrum disorder (ASD). Previous mouse studies have investigated the role of ECS in several behavioral domains; however, none of them has performed an extensive assessment of social and communication behaviors, that is, the main core features of ASD. This study employed a mouse line lacking the primary endocannabinoid receptor (CB1r) and characterized ultrasonic communication and social interaction in CB1−/−, CB1+/−, and CB1+/+ males and females. Quantitative and qualitative alterations in ultrasonic vocalizations (USVs) were observed in CB1 null mice both during early development (i.e., between postnatal days 4 and 10), and at adulthood (i.e., at 3 months of age). Adult mutants also showed marked deficits in social interest in the three‐chamber test and social investigation in the direct social interaction test. These behavioral alterations were mostly observe...

French Journal of Psychiatry, 2018

Alcoholism: Clinical and Experimental Research, 2020

Background: Pleiotrophin (PTN) and Midkine (MK) are cytokines that are upregulated in the prefron... more Background: Pleiotrophin (PTN) and Midkine (MK) are cytokines that are upregulated in the prefrontal cortex (PFC) after alcohol administration and have been shown to reduce alcohol intake and reward. Both cytokines are endogenous inhibitors of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ (a.k.a. PTPRZ1). Recently, a new compound named MY10 was designed with the aim of mimicking the activity of PTN and MK. MY10 has already shown promising results regulating alcohol-related behaviors in mice. Methods: We have now tested the effects of MY10 on alcohol operant self-administration and Drinking In the Dark-Multiple Scheduled Access (DID-MSA) paradigms in rats. Gene expression of relevant genes in the PTN/MK signalling pathway in the PFC was analyzed by real-time PCR. Results: MY10, at the highest dose tested (100 mg•kg -1 ), reduced alcohol consumption in the alcohol operant self-administration paradigm (p=0.040). In the DID-MSA paradigm, rats drank significantly less alcohol (p=0.019) and showed a significant decrease in alcohol preference (p=0.002). We observed that the longer the exposure to alcohol, the greater the suppressing effects of MY10 on alcohol consumption. It was demonstrated that the effects of MY10 were specific to alcohol since saccharin intake was not affected by MY10 (p=0.804). MY10 prevented the alcoholinduced downregulation of Ptprz1 (p=0.004) and Anaplastic Lymphoma kinase (Alk) (p=0.013) expression. Our results support and provide further evidence regarding the efficacy of MY10 on alcohol-related behaviors and suggest the consideration of the blockade of RPTPβ/ζ as a target for reducing excessive alcohol consumption.

Is R(+)‐Baclofen the best option for the future of Baclofen in alcohol dependence pharmacotherapy? Insights from the preclinical side

Addiction Biology, 2020

For several decades, studies conducted to evaluate the efficacy of RS(±)‐Baclofen in the treatmen... more For several decades, studies conducted to evaluate the efficacy of RS(±)‐Baclofen in the treatment of alcohol dependence yielded contrasting results. Human and animal studies recently questioned the use of the racemic drug in patients since a potential important role of the different enantiomers has been revealed with an efficacy thought to reside with the active R(+)‐enantiomer. Here we conducted experiments in the postdependent rat model of alcohol dependence to compare the efficacy of R(+)‐Baclofen or S(−)‐Baclofen to that of RS(±)‐Baclofen on ethanol intake, seeking, and relapse. R(+)‐Baclofen was more effective than RS(±)‐Baclofen in reducing ethanol intake and seeking during acute withdrawal and during relapse after abstinence. We also used an original population approach in order to identify drug responders. We found a significant proportion of responders to S(−)‐Baclofen and RS(±)‐Baclofen, displaying an increase in ethanol intake, and this increasing effect on alcohol intak...

Nutrients, 2018

Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been asso... more Alzheimer’s disease (AD) is the main cause of dementia and cognitive impairment. It has been associated with a significant diminution of omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) levels in the brain. Clinical trials with DHA as a treatment in neurological diseases have shown inconsistent results. Previously, we reported that the presence of phytanic acid (PhA) in standard DHA compositions could be blunting DHA’s beneficial effects. Therefore, we aimed to analyze the effects of a low PhA-concentrated DHA and a standard PhA-concentrated DHA in Apolipoprotein E knockout (ApoE−/−) mice. Behavioral tests and protein expression of pro-inflammatory, pro-oxidant, antioxidant factors, and AD-related mediators were evaluated. Low PhA-concentrated DHA decreased Aβ, ß-amyloid precursor protein (APP), p-tau, Ca2+/calmodulin-dependent protein kinase II (CAMKII), caspase 3, and catalase, and increased brain derived neurotrophic factor (BDNF) when compared to standard PhA-concen...

Behavioural Brain Research, 2019

Although the genetic influence on global stopping has been extensively investigated, little is kn... more Although the genetic influence on global stopping has been extensively investigated, little is known about the genetic contribution to other more complex forms of inhibitory control such as selective stopping. The selectivity of inhibitory control can be assessed by using the stimulus-selective stop-signal task. Notably, recent behavioural and neural evidence indicates that individuals can adopt selective but also non-selective stopping strategies to solve it. This study aimed to investigate for the first time the influence of two relevant dopaminergic polymorphisms (in COMT and DRD2 genes) on stimulus-selective stopping in a sample of 529 adults. Results showed that although none of these polymorphisms (neither individually nor in combination) modulate the latency of the stop process in each strategy (the stop-signal reaction time), the choice of strategy was influenced by their interaction. These results suggest that dopaminergic polymorphisms might influence strategy adoption in selective stopping paradigms, which constitutes a novel finding.

Addiction Biology, 2018

Binge drinking (BD) is often defined as a large amount of alcohol consumed in a ‘short’ period of... more Binge drinking (BD) is often defined as a large amount of alcohol consumed in a ‘short’ period of time or ‘per occasion’. In clinical research, few researchers have included the notion of ‘speed of drinking’ in the definition of BD. Here, we aimed to describe a novel pre‐clinical model based on voluntary operant BD, which included both the quantity of alcohol and the rapidity of consumption. In adult Long–Evans male rats, we induced BD by regularly decreasing the duration of ethanol self‐administration from 1‐hour to 15‐minute sessions. We compared the behavioral consequences of BD with the behaviors of rats subjected to moderate drinking or heavy drinking (HD). We found that, despite high ethanol consumption levels (1.2 g/kg/15 minutes), the total amounts consumed were insufficient to differentiate HD from BD. However, consumption speed could distinguish between these groups. The motivation to consume was higher in BD than in HD rats. After BD, we observed alterations in locomotor ...

Addiction Biology, 2017

Mixing alcohol with caffeinated energy drinks is a common practice, especially among young people... more Mixing alcohol with caffeinated energy drinks is a common practice, especially among young people. In humans, the research on this issue has mainly focused on the use of the mass‐marketed energy drinks themselves, whereas in animal models, it has focused on the individual effects of their active ingredients (i.e. caffeine). Here, we have characterized how Red Bull®, one of the most consumed caffeinated energy drink worldwide, modulates operant alcohol self‐administration in Wistar rats. We found that animals readily and steadily responded for Red Bull (mean: 90 responses, 30 minutes and fixed‐ratio 1), which was accompanied by locomotor stimulating effects (26 percent increase). The higher the concentration of alcohol (3–20 percent), the higher the consumption of alcohol (g/kg) and associated blood alcohol levels (91.76 percent) in the mixed Red Bull–alcohol group (60 percent increase). Blood caffeine levels in the Red Bull group were 4.69 μg/ml and 1.31 μg/ml in the Red Bull–alcoho...

Stem Cells, 2016

The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracell... more The phosphodiesterase 7 (PDE7) enzyme is one of the enzymes responsible for controlling intracellular levels of cyclic adenosine 3′,5′-monophosphate in the immune and central nervous system. We have previously shown that inhibitors of this enzyme are potent neuroprotective and anti-inflammatory agents. In addition, we also demonstrated that PDE7 inhibition induces endogenous neuroregenerative processes toward a dopaminergic phenotype. Here, we show that PDE7 inhibition controls stem cell expansion in the subgranular zone of the dentate gyrus of the hippocampus (SGZ) and the subventricular zone (SVZ) in the adult rat brain. Neurospheres cultures obtained from SGZ and SVZ of adult rats treated with PDE7 inhibitors presented an increased proliferation and neuronal differentiation compared to control cultures. PDE7 inhibitors treatment of neurospheres cultures also resulted in an increase of the levels of phosphorylated cAMP response element binding protein, suggesting that their effect...