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See detailExercise against cocaine sensitization in mice: a [18F]fallypride micro-PET study.
Becker, Guillaume ULiege; Lespine, Louis-Ferdinand ULiege; Bahri, Mohamed Ali ULiege et al

in Brain Communications (2021)

Wheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioural markers of vulnerability to addictive properties of various drugs of ... [more ▼]

Wheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioural markers of vulnerability to addictive properties of various drugs of abuse including cocaine. However, neurobiological mechanisms underpinning this protective effect are far from fully characterized. Here, 28-day-old female C57BL/6J mice were housed with (n=48) or without (n=48) a running wheel for 6 weeks before being tested for acute locomotor responsiveness and initiation of locomotor sensitization to intraperitoneal injections of 8 mg/kg cocaine. The long-term expression of sensitization took place 3 weeks after the last session. On the day after, all mice underwent a micro-PET imaging session with [18F]fallypride radiotracer (dopamine 2/3 receptors antagonist). Exercised mice were less sensitive to acute and sensitized cocaine hyperlocomotor effects, such attenuation being particularly well-marked for long-term expression of sensitization (η²p = 0.262). Chronic administration of cocaine was associated with a clear-cut increase of [18F]fallypride binding potential in mouse striatum (η²p = 0.170) while wheel-running exercise was associated with a moderate decrease in dopamine 2/3 receptors density in striatum (η²p = 0.075), a mechanism that might contribute to protective properties of exercise against drugs of abuse vulnerability. [less ▲]

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See detailAre the studies (tests) assessing the efficacy of the treatments of the alcoholdeprivation effect underpowered?
Léonard, François ULiege; Tirelli, Ezio ULiege

Poster (2021, May 28)

While adequate power and sample sizes are indispensable for the detection (by the statistical test) of a meaningful effect size (ES), many published studies in psychology do not describe sample-size ... [more ▼]

While adequate power and sample sizes are indispensable for the detection (by the statistical test) of a meaningful effect size (ES), many published studies in psychology do not describe sample-size calculation (SSC), which weakens the study methodological quality. Omission of SSC is often associated with a lack of prospective power, which exaggerates observed ES and increases the False Report Probability (FRP), thereby jeopardizing results reproducibility. Our purpose is to investigate in which extent this practice concerns the literature assessing the efficacy of the psychological and pharmacological treatments of the alcohol-deprivation effect (operationalized in an animal model). We will firstly select articles published from 1993 to 2020 using the database PubMed and check whether they mention a SSC. We will then classify the articles mentioning a SSC according to five components of a complete description of SSC (ex. power analysis with or without details). We will also check whether the hypothetical ES (used to determine sample sizes) is justified and the observed ES interpreted (discussion). Thereupon, in order to assess a possible ES overestimation in the selected literature, we will examine the relationship between the observed ES and the sample sizes. We will compute the “power-to-detect” of each relevant statistical test using small, medium and large ES (classifications). Finally, we will compute the FRP and the True Discovery Rate using a risk alpha of 1, 2.5 or 5%, the median “power-to-detect” and a representative range of pre-study odds (from 0.01 to 0.99), according to Ioannidis (2005) and Szucs & Ioannidis (2017). [less ▲]

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See detailReporting quality of the literature on the pharmacological and psychological treatments of the alcohol-deprivation effect
Léonard, François ULiege; Monseur, Christian ULiege; Tirelli, Ezio ULiege

Poster (2021, May 28)

Adequate reporting practices are essential to transparent and reproducible research. A lack of adequate reporting could notably reflect methodological deficiencies, a rampant problem in experimental and ... [more ▼]

Adequate reporting practices are essential to transparent and reproducible research. A lack of adequate reporting could notably reflect methodological deficiencies, a rampant problem in experimental and biological psychology. We assessed the reporting quality in the literature on pharmacological and psychological treatments of alcohol-deprivation effect (ADE), a popular behavioral animal model of alcohol relapse. A literature search on PubMed yielded 154 titles among which we extracted 68 articles meeting the inclusion criteria. We evaluated these articles according the reporting guide ARRIVE 2.0 that comprises 54 items, each of which being coded as properly reported or not. On a 55-point scale (including 0), the median reporting score was 27 [IQR: 24; 29.25]. The articles reporting scores moderately increased from 1993 to 2020, as suggested by a LOWESS regression generated from 100 000 bootstraps, the R² being 0.158 [CI95%: 0.036; 0.316]. This trend was supported by the comparison, using a two-sided Mann-Whitney U test, of the scores derived from the articles published before 2010 (first publication of ARRIVE) and those published after 2012, which resulted in a 9.61% increase with a moderate effect size r of 0.34 [CI95: 0.11; 0.55]. Our results generalize the low quality of reporting practices found in several fields of experimental and biological psychology to the field of ADE. Although we found a measurable and encouraging increase in the quality of reporting, there is still much room for improvement. [less ▲]

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See detailPower and True Report Probability in the Literature on Mice Nicotine Conditioned Place Preference
Léonard, François ULiege; Tirelli, Ezio ULiege

Poster (2021, May 28)

A lack of prospective power and use of effect sizes in the literature of various fields have been revealed and characterized over the years, giving rise to serious doubts on the reproducibility of many ... [more ▼]

A lack of prospective power and use of effect sizes in the literature of various fields have been revealed and characterized over the years, giving rise to serious doubts on the reproducibility of many scientific results (Button & al. 2013, Nat.Rev.Neurosci. 14:365-376; Cohen 1962, Abnorm.Psychol. 65:145-153). To our knowledge, no study has address this problem in the field of experimental psychopharmacology using animal models. The articles were identified in PubMed. The sample size, the type of statistical test, its result, degrees of freedom and pvalue were recorded. We then computed the individual and the median prospective powers for 6 possible effect sizes (Cohen’s d: 0.01, 0.2, 0.5, 0.8, 1.2, 2). The TRP was computed from the median power, type-I error rate and the plausibility (prior probability). Amongst 139 articles, only 47 met our inclusion criteria for 109 statistical tests. In this sample, 77.57% of tests were significant. The median powers for small (0.2), medium (0.5) and large (0.8) effect sizes in F test were 9.56% [IQR 7.96%-11.5%], 34.45% [IQR 24.61%-47.01%] and 70.46% [IQR 52.92%-85.91%]. None of these numbers reached the recommended minimal prospective power of 80%. A 50% hypothetical plausibility yielded TRPs of 48.9%, 77.5%, and 87.6% for small, medium and large effect sizes. For a plausibility of 10%, the TRP were 16.1%, 40.8% and 58.5%. These results generalize to a subfield of animal-model experimental psychopharmacoloy (nicotine CPP in mice) the lack of power reported in the litterature of several neurobehavioural and psychological disciplines. [less ▲]

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See detailThe methodological quality of meta-analyses indexed in PsycINFO: leads for enhancements – a meta-epidemiological study
Leclercq, Victoria ULiege; Beaudart, Charlotte ULiege; Ajamieh, Sara ULiege et al

in BMJ Open (2020), 10

Objectives Meta-analyses (MAs) are often used because they are lauded to provide robust evidence that synthesises information from multiple studies. However, the validity of MA conclusions relies on the ... [more ▼]

Objectives Meta-analyses (MAs) are often used because they are lauded to provide robust evidence that synthesises information from multiple studies. However, the validity of MA conclusions relies on the procedural rigour applied by the authors. Therefore, this meta-research study aims to characterise the methodological quality and meta-analytic practices of MAs indexed in PsycINFO. Design A meta-epidemiological study. Participants We evaluated a random sample of 206 MAs indexed in the PsycINFO database in 2016. Primary and secondary outcomes Two authors independently extracted the methodological characteristics of all MAs and checked their quality according to the 16 items of the A MeaSurement Tool to Assess systematic Reviews (AMSTAR2) tool for MA critical appraisal. Moreover, we investigated the effect of mentioning Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) on the methodological quality of MAs. Results According to AMSTAR2 criteria, 95% of the 206 MAs were rated as critically low quality. Statistical methods were appropriate and publication bias was well evaluated in 87% and 70% of the MAs, respectively. However, much improvement is needed in data collection and analysis: only 11% of MAs published a research protocol, 44% had a comprehensive literature search strategy, 37% assessed and 29% interpreted the risk of bias in the individual included studies, and 11% presented a list of excluded studies. Interestingly, the explicit mentioning of PRISMA suggested a positive influence on the methodological quality of MAs. Conclusion The methodological quality of MAs in our sample was critically low according to the AMSTAR2 criteria. Some efforts to tremendously improve the methodological quality of MAs could increase their robustness and reliability. [less ▲]

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See detailBest-worst scaling identified adequate statistical methods and literature search as the most important items of AMSTAR2 (A measurement tool to assess systematic reviews)
Leclercq, Victoria ULiege; Hiligsmann, Mickaël ULiege; Parisi, Gianni ULiege et al

in Journal of Clinical Epidemiology (2020), 128

Objective: To assess the relative importance of A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) items. Study design and setting: A best-worst scaling object case was conducted among a sample ... [more ▼]

Objective: To assess the relative importance of A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR2) items. Study design and setting: A best-worst scaling object case was conducted among a sample of experts in the field of systematic reviews (SRs) and meta-analyses (MAs). Respondents were asked in a series of 15 choice tasks to choose the most and the least important item from a set of four items from the master list, which included the 16 AMSTAR2 items. Hierarchical Bayes analysis was used to generate the relative importance score for each item. Results: The most important items highlighted by our 242 experts to conduct overview of reviews and critically assess SRs/MAs were the appropriateness of statistical analyses and adequacy of the literature search, followed by items regarding the assessment of risk of bias, the research protocol, and the assessment of heterogeneity (relative importance score >6.5). Items related to funding sources and the assessment of study selection and data extraction in duplicate were rated as least important. Conclusion: Although all AMSTAR2 items can be considered as important, our results highlighted the importance of keeping the two items (the appropriateness of statistical analyses and the adequacy of the literature search) among the critical items proposed by AMSTAR2 to critically appraise SRs/MAs. [less ▲]

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See detailPsychometric measurements of AMSTAR 2 in a sample of meta-analyses indexed in PsycINFO
Leclercq, Victoria ULiege; Beaudart, Charlotte ULiege; Tirelli, Ezio ULiege et al

in Journal of Clinical Epidemiology (2020), 119

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See detailLong-term exposure to daily ethanol injections in DBA/2J and Swiss mice: Lessons for the interpretation of ethanol sensitization
Didone, Vincent ULiege; Van Ingelgom, Théo ULiege; Tirelli, Ezio ULiege et al

in PLoS ONE (2019), 14(11)

Most mice ethanol sensitization studies focused on neurobiology at the expense of its behavioral characterization. Furthermore, relatively short ethanol exposures (10 to 20 injections) were used in these ... [more ▼]

Most mice ethanol sensitization studies focused on neurobiology at the expense of its behavioral characterization. Furthermore, relatively short ethanol exposures (10 to 20 injections) were used in these studies. The first aim of the present study is to better characterize the development and expression of ethanol sensitization after an extended exposure of 45 daily injections. In some previous studies, mice were classified as “respondent” and “resistant” to ethanol sensitization. The second aim of the present study is to test the long-term reliability of such categorizations and the consequences of their use on the interpretation of the ethanol sensitization results. Swiss and DBA/2J female mice received 45 consecutive daily ethanol administrations (respectively 2.5 and 2.0 g/kg) and their locomotor activity was daily recorded to test the development of ethanol sensitization. At the end of the procedure, a challenge test assessed the inter-group ethanol sensitization. The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA/2J mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. Remarkably, ethanol sensitization after such a long daily ethanol treatment resulted in both an upward shift of the magnitude of ethanol stimulant effects and a prolongation of these effects in time (up to 30 minutes). Mice classified as “resistant to ethanol sensitization” according to previous studies developed very significant levels of ethanol sensitization when tested after 45 ethanol injections and are best described as showing a delayed development of ethanol sensitization. Furthermore, mice classified as respondent or resistant to ethanol sensitization also differ in their acute response to ethanol, such that it is difficult to ascertain whether these classifications are specifically related to the sensitization process. [less ▲]

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See detailCharacterization of the behavioral sensitization and the conditioned response induced by long-term exposure to alcohol in DBA/2J and Swiss mice.
Didone, Vincent ULiege; Van Ingelgom, Théo ULiege; Tirelli, Ezio ULiege et al

Poster (2019, September 23)

Repeated administrations of addictive drugs induce gradual changes in some of their behavioral effects. This phenomenon is called “behavioral sensitization”. In laboratory rodents, drug-induced behavioral ... [more ▼]

Repeated administrations of addictive drugs induce gradual changes in some of their behavioral effects. This phenomenon is called “behavioral sensitization”. In laboratory rodents, drug-induced behavioral sensitization is generally modeled as a progressive increase in the locomotor stimulant effects over repeated administrations of the same drug dose. Chronic exposure to ethanol has been shown to induce a strong and robust sensitization in mice. Very few studies were published on the behavioral aspects of ethanol-induced sensitization, especially regarding the procedural and environmental parameters influencing its development and expression (duration of the process). Therefore, little is known about the time course of ethanol sensitization after an extensive exposure exceeding a few days. The first aim of the present study was to better characterize the development and expression of ethanol sensitization after an extended exposure to 45 daily injections. Does ethanol sensitization continue to develop at the same rate after the first few days of ethanol administrations ? Does it reach a ceiling effect? Does it even start to decline after reaching a peak level? The second aim was to test whether ethanol sensitization results in a conditioned increase in locomotor activity when sensitized mice are tested after a saline injection in the testing environment. The results of the present study show that ethanol sensitization continues to develop beyond 20 days to reach maximal levels after about 25 injections in DBA2/j mice and 40 injections in Swiss mice, although the core phase of the development of ethanol sensitization occurred in both strains during the first 20 days. The present results extend previous reports indicating that sensitization to the stimulant effects of ethanol does not induce an excitatory conditioned response, even after 46 associations of a specific context with ethanol injections. The extensive exposition to ethanol in the present study makes it very unlikely that the lack of conditioned response was due to an insufficient pairing of the test context with ethanol injections. [less ▲]

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See detailMeta-analyses indexed in PsycINFO had a better completeness of reporting when they mention PRISMA
Leclercq, Victoria ULiege; Beaudart, Charlotte ULiege; Ajamieh, Sara ULiege et al

in Journal of Clinical Epidemiology (2019), 115

Objectives:To investigate the effect of the explicit mention of PRISMA, a statement designed to help authors report meta-analyses(MAs), on the reporting completeness of MAs.

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See detailAnxiety-like features and spatial memory problems as a consequence of hippocampal SV2A expression.
Serrano Navacerrada, Maria Elisa ULiege; Bartholomé, Odile ULiege; Van den Ackerveken, Priscillia et al

in PLoS ONE (2019)

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose presence is reduced both in animal models and in patients with chronic epilepsy. Besides its implication in the epileptic process ... [more ▼]

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose presence is reduced both in animal models and in patients with chronic epilepsy. Besides its implication in the epileptic process, the behavioural consequences of the changes in its expression remain unclear. The purpose of our research is to better understand the possible role(s) of this protein through the phenotype of cKO (Grik4 Cre+/-, SV2A lox/lox) mice, male and female, which present a specific decrease of SV2A expression levels in the hippocampal glutamatergic neurons but without any epileptic seizures. In this study, we compare the cKO mice with cHZ (Grik4 Cre+/-, SV2A lox/+) and WT (Grik4 Cre+/+, SV2A lox/lox) mice through a battery of tests, used to evaluate different features: the anxiety-related features (Elevated Plus Maze), the locomotor activity (Activity Chambers), the contextual fear-related memory (Contextual Fear Conditioning), and the spatial memory (Barnes Maze). Our results showed statistically significant differences in the habituation to a new environment, an increase in the anxiety levels and spatial memory deficit in the cHZ and cKO groups, compared to the WT group. No statistically significant differences due to the genotype appeared in the spontaneous locomotor activity or the fear-linked memory. However, sexual differences were observed in this last feature. These results highlight not only an important role of the SV2A protein in the cognitive and anxiety problems typically encountered in epileptic patients, but also a possible role in the symptomatology of other neurodegenerative diseases, such as the Alzheimer’s disease. [less ▲]

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See detailThe explicit use of PRISMA and its effect on the reporting completeness of meta-analyses in the field of behavioral and social sciences
Leclercq, Victoria ULiege; Beaudart, Charlotte ULiege; Ajamieh, Sara ULiege et al

Poster (2019, May 14)

Objectives: To investigate the effect of the explicit use of PRISMA, a statement designed to help authors to report meta-analyses (MAs), on the reporting quality of MAs in behavioral and social sciences ... [more ▼]

Objectives: To investigate the effect of the explicit use of PRISMA, a statement designed to help authors to report meta-analyses (MAs), on the reporting quality of MAs in behavioral and social sciences. Methods: We evaluated a random sample of 207 MAs indexed in PsycINFO in 2016; 100 explicitly used PRISMA and 107 did not. Two authors independently checked the 27 PRISMA items and extracted factors that could potentially be associated with reporting quality. Results: From our 207 MAs, perfect adherence to PRISMA was found in less than 4%, of which 87% explicitly used PRISMA. The following items were significantly more frequently encountered in MAs that explicitly used PRISMA: structured summary, protocol and registration, information sources, search strategy, study characteristics, results of individual studies, funding, study selection, risk of bias in individual study and bias across studies. The journals’ impact factors, the endorsement of PRISMA by the journal, the number of authors, the country of the first author, the open access of the article and the design of the studies were significantly and positively associated with the explicit PRISMA use. Conclusions: Even if far from optimal, the explicit use of PRISMA has a positive influence on the reporting completeness of MAs. [less ▲]

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See detailThe methodological quality of meta-analyses in behavioral and social sciences: leads for enhancements according to AMSTAR 2
Leclercq, Victoria ULiege; Beaudart, Charlotte ULiege; Ajamieh, Sara ULiege et al

Poster (2019, May 14)

Objectives: To investigate the methodological quality in meta-analyses (MAs) published in behavioral and social sciences. Methods: We evaluated a random sample of 207 MAs indexed in PsycINFO database in ... [more ▼]

Objectives: To investigate the methodological quality in meta-analyses (MAs) published in behavioral and social sciences. Methods: We evaluated a random sample of 207 MAs indexed in PsycINFO database in 2016. Two authors independently extracted methodologic characteristics of all MAs with the 16 items of AMSTAR2 (A MeaSurement Tool to Assess systematic Reviews 2). AMSTAR2 allows to assess the methodological quality of MAs that classifies them in 4 categories: critically low, low, moderate and high. Results: From the 207 MAs, according to AMSTAR2 criteria, 95% of MAs were rated as critically low. Statistical methods were appropriate and publication bias well evaluated in respectively 87% and 70% of the MAs. However, much improvement is needed in data collection and analysis: Publication of the research protocol (in 11% of MAs), comprehensive literature search strategy (44%), assessment (37%) and interpretation (29%) of risk of bias in individual included studies and presentation of excluded studies (11%). Conclusions: The methodological quality of MAs of our sample was critically low, according to AMSTAR2 criteria. Some efforts could improve tremendously the methodological quality of behavioral and social sciences MAs and thus gain in robustness and reliability. [less ▲]

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See detailInvestigating the reciprocal relationships between locomotor sensitization to ethanol and PTSD-like clusters in DBA/2J mice.
Matonda Ma Nzuzi, ULiege; Didone, Vincent ULiege; Seutin, Vincent ULiege et al

in Behavioural Brain Research (2019)

BACKGROUND: Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are two conditions that co-occur frequently. The mechanistic explanations of this co-morbidity are still unclear. The goal ... [more ▼]

BACKGROUND: Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are two conditions that co-occur frequently. The mechanistic explanations of this co-morbidity are still unclear. The goal of this study was twofold. First to investigate whether PTSD reduces the threshold for the acquisition of ethanol sensitization in an animal model of PTSD. Then to investigate whether ethanol sensitization modulates the expression of PTSD. METHODS: 152 female inbred DBA/2 J mice were submitted to an inescapable footshock paradigm to induce a PTSD-like condition (PTSDLC) and to a paradigm of locomotor sensitization to ethanol. In a first experiment, mice were submitted to the PTSDLC and then repeatedly injected with either saline, 1 g/kg ethanol or 2 g/kg ethanol. Their sensitization to the locomotor stimulant effects of ethanol was then tested in an open field. In a second experiment, mice were first sensitized to the locomotor stimulant effects of ethanol and then tested for their behavioral response to PTSDLC. RESULTS: In the first experiment, PTSDLC failed to induce a significant locomotor sensitization at the subthreshold dose of 1 g/kg ethanol. However, with 2 g/kg ethanol, a stronger ethanol sensitization was observed in mice submitted to the footshock relative to the control group. In the second experiment, ethanol sensitization increased only some of the behavioral clusters of PTSDLC, namely the fear generalization in a new context. CONCLUSION: PTSDLC did not reduce the dose threshold for the acquisition of ethanol sensitization but strengthened the development of ethanol sensitization with effective doses. This suggests that PTSD might interact with one of the mechanisms underlying the development of alcohol sensitization. When the relationship between ethanol sensitization and PTSDLC is tested in the reverse direction, the present study only shows a significant effect of ethanol administration on the "sensitized fear" PTSD cluster. [less ▲]

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See detailWheel-running exercise before and during gestation against acute and sensitized cocaine psychomotor-activation in offspring.
Lespine, Louis-Ferdinand ULiege; Plenevaux, Alain ULiege; Tirelli, Ezio ULiege

in Behavioural Brain Research (2019), 363

While animal research has consistently reported preventive effects of exercise against drug abuse vulnerability, little is known about the influence of the developmental stage during which exercise is ... [more ▼]

While animal research has consistently reported preventive effects of exercise against drug abuse vulnerability, little is known about the influence of the developmental stage during which exercise is displayed on addictive drugs responsiveness. This study aimed to determine whether prenatal exercise could attenuate acute cocaine reactivity and psychomotor sensitization in youth offspring. We used a split-plot factorial design where C57BL/6 J females were randomly assigned into sedentary or exercised (wheel-running) conditions before and during gestation, the wheels being removed on gestational day 18. Offspring were weaned, gendered and individually housed on 24–28 days old. At 38–42 days old, they were tested for their acute psychomotor responsiveness to 8 mg/kg cocaine and their initiation of sensitization over 8 additional once-daily administrations, the long-term expression of sensitization occurring 30 days later. Adolescent females born from exercised mothers were much less responsive to the acute psychomotor-stimulating effect of cocaine than those born from sedentary mothers (d=0.75, p=0.02), whereas there was no evidence for such a difference in males (d=0.34, p=0.17). However, we did not find sizeable attenuating effects of prenatal exercise on the initiation and the long-term expression of the psychomotor-activating effect of cocaine, in either sex (Cohen’s ds varying from −0.13 to 0.39). These results suggest that prenatal exercise may induce initial protection against cocaine responsiveness in youth females, a finding that warrants further research. [less ▲]

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See detailNo evidence that wheel-running exercise impacts cocaine conditioned place preference in male C57BL/6J mice
Lespine, Louis-Ferdinand ULiege; Tirelli, Ezio ULiege

in Behavioural Brain Research (2019), 365

Wheel-running in rodents can mitigate addiction-related effects of drugs of abuse like cocaine. However, conditioned place preference (CPP) experiments have reported conflicting results, a situation ... [more ▼]

Wheel-running in rodents can mitigate addiction-related effects of drugs of abuse like cocaine. However, conditioned place preference (CPP) experiments have reported conflicting results, a situation warranting further studies. Our purpose was to test whether wheel-running exercise during adolescence could impact the formation and long-term retention of CPP to cocaine in mice. Male C57BL/6 J mice were individually housed either with (n = 32) or without (n = 32) a running wheel from the age of 35 days. Behavioral testing began 3 weeks after such housing, mice underwent a baseline session followed by 10 once-daily conditioning sessions receiving peritoneal injections of 10 mg/kg cocaine and saline on alternate days (n = 16), control mice receiving saline every day (n = 16). One and 21 days after the last conditioning session, they were tested for CPP. Both groups exhibited comparable well-marked cocaine-induced CPP in both post-conditioning tests resulting in a negligible interaction between housing and the pharmacological treatment (η²p < 0.01). These results, along with the discrepancy found in the literature, question the nature (and the robustness) of the effects that exercise induces on CPP to cocaine. © 2019 [less ▲]

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See detailEffects of exposure to an EDC mixture on the pubertal timing through a maternal behavioral epigenetic multigenerational transmission
Lopez Rodriguez, David ULiege; Delli, Virginia; GERARD, Arlette ULiege et al

Conference (2019)

Endocrine disrupting chemicals (EDCs) are today a rising public health challenge because of their ubiquity and presence in complex mixtures and their effects on the developing body throughout generations ... [more ▼]

Endocrine disrupting chemicals (EDCs) are today a rising public health challenge because of their ubiquity and presence in complex mixtures and their effects on the developing body throughout generations. We aim at studying the effect of a mixture of EDCs on female sexual development during 3 generations of females after exposure and determine whether an epigenetic hypothalamic mechanism is involved in those effects. Female rats were orally exposed from 2 weeks before gestation until weaning to corn oil or a mixture of 14 anti-androgenic and estrogenic EDCs at low doses (F0 generation). Sexual development (vaginal opening, GnRH interpulse interval and estrous cyclicity) as well as maternal behavior were measured from F1 to F3 generation. An RNAseq was carry out using mediobasal hypothalamus from females at P21 from the F1 and F3 generation to decipher targets of the exposure, then validated by RT-PCR and studied for epigenetic modifications by ChIP. F2 and F3 females showed a delayed puberty (delayed VO) and a decrease in the percentage of females having regular estrous cycles, characterized by a significant increase in the time spent in estrus and decreased time spent in diestrus. A hypothalamic epigenetic mechanism is known to be involved in the onset of puberty. We have observed both transcriptional and histone epigenetic alterations in genes involved in estrogen (ESR1), glutamtergic (GRIN2Dà and dopamine (TH and DRD1) signaling as well as in glucocorticoid activity (NR3C1 and CRH), kisspeptin (KISS1) and oxytocin (OXT). We have as well observed that F1 females, exposed in utero, which shows a decrease in TH mRNA expression spent less time licking and more time resting alone. Those modifications on maternal behavior are known to be transmitted through generations. Overall, data shows that gestational exposure to an EDCs mixture can affect maternal behavior and sexual development during several generations. The F1 alteration of maternal behavior caused by in utero exposure to the mixture of EDCs trigger a multigenerational transmission of the phenotype and an induces an altered epigenetic reprogramming if the hypothalamus. [less ▲]

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See detailEDC mixture disrupts maternal behavior and the hypothalamic control of puberty transgenerationally through epigenetic mechanisms.
Lopez Rodriguez, David ULiege; Alwin, Carlos Francisco; GERARD, Arlette ULiege et al

Poster (2019)

Endocrine disrupting chemicals (EDCs) are a rising concern for public health due to their ubiquity as complex mixtures. Our goal was to study the effect of an EDC mixture on female sexual development ... [more ▼]

Endocrine disrupting chemicals (EDCs) are a rising concern for public health due to their ubiquity as complex mixtures. Our goal was to study the effect of an EDC mixture on female sexual development during 3 generations. Female rats (F0 generation) were orally exposed to a mixture of 13 anti-androgenic and estrogenic EDCs or corn oil for 2 weeks before gestation until weaning. The mixture was composed of plasticizers, fungicides/pesticides, UV filters, parabens and acetaminophen at doses representing human exposure. Sexual development (vaginal opening, GnRH interpulse-interval, estrous cyclicity and folliculogenesis) and maternal behavior were studied from F0 to F3 generations. At PND21, mediobasal hypothalamus of the F1 and F3 were removed for gene expression, histone modifications and DNA methylation analysis of target genes. F2 and F3 females showed delayed vaginal opening, decreased percentage of regular estrous cycle, decreased GnRH interpulse interval and altered late stage folliculogenesis. F1 and F2 females showed decreased maternal licking behavior while spending more time resting alone. The phenotype was associated with transcriptional and epigenetic alterations of hypothalamic genes involved in reproductive competence and behavior like kisspeptin (Kiss1), oxytocin (Oxt), estrogen (Esr1), glutamate (Grin2d), dopamine signaling (Th) as well as glucocorticoid activity (Nr3c1 and Crh). We have found alterations in repressive (H3K27me3, H3K9me3) or active (H3K4me3, H3K9ac) histone marks concomitant with transcriptional activity. Overall, gestational and lactational exposure to an environmentally relevant EDC mixture transgenerationally affects sexual development throughout epigenetic reprogramming of the hypothalamic control of puberty. Such effects could be mediated by alterations of maternal behavior. [less ▲]

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