References of "Tirelli, Ezio"
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See detailNeuro-functional correlates of the protective effects of exercise against cocaine sensitization and dopamine D2 receptors density: a [18F]Fallypride microPET study.
Becker, Guillaume ULiege; Lespine, Louis-Ferdinand ULiege; Serrano Navacerrada, Maria Elisa ULiege et al

in Molecular Imaging and Biology (in press)

Preclinical studies suggest that free access to a running wheel can attenuate behavioural effects of addictive drugs such as psychomotor sensitization to cocaine in rodents. This phenomenon has an ... [more ▼]

Preclinical studies suggest that free access to a running wheel can attenuate behavioural effects of addictive drugs such as psychomotor sensitization to cocaine in rodents. This phenomenon has an integral role in the process of drug addiction in craving and relapse (Steketee and Kalivas, 2011). Free wheel-running was recently shown to be efficacious at preventing the initiation or the long-term expression of psychomotor sensitization to cocaine in mice or rats (Diaz et al., 2013; Geuzaine and Tirelli, 2014). In the present study, we investigated the neuro-functional correlates of the protection against psychomotor sensitization to cocaine afforded by free wheel-running on dopaminergic neurotransmission, using microPET imaging with [18F]Fallypride, a Dopamine 2 receptor (D2R) antagonist. Sixty-four 28-day-old female C57BL/6J mice were randomly assigned to one of the two housing conditions, defined by the presence or the absence of a running wheel in the cage over a 6-week pre-testing period. Since mice from the two types of housing received either saline (controls) or cocaine (8 mg/kg, i.p.) during testing (9 once-daily sessions to establish sensitization plus 1 single session to test its expression), a basic 2x2 randomized blocks design was generated (2-way ANOVA and planned comparisons; n=10). Experimentation lasted 85 days, with a 42-day period of pre-testing and a 3-week interval preceding the test for long-term expression of sensitization (LTES). All mice underwent a microPET (Focus 120, Siemens) the day after the LTES. The microPET protocol consisted of a 60 min. dynamic acquisition after the injection of 10 MBq of [18F]Fallypride in the tail vein. Wheel-running strongly and significantly attenuated LTES (interaction) to cocaine (Cohen’s d=1.63; t(21)=3.75, p<.001) and cocaine-treated mice exhibited a clear-cut and significant increase (main effect) of the [18F]Fallypride BP (d=0.88, t(31)=2.45, p =.02). Wheel-running induced an overall moderate-sized decrease (main effect) of the [18F]Fallypride BP, but without achieving statistical significance (d=0.64, t(31)=1.79, p =.08). These findings suggest that LTES is associated with an increase of the [18F]Fallypride BP in the mouse striatum, probably reflecting an increase in postsynaptic D2R density in this region. Also, the protecting effect of free running on psychomotor sensitization goes together with a decrease in D2R density in the striatum of exercised mice. We intend to complement the present study with an identical experiment to reach a total number of 80 mice (n=20). This will confer to our study a sufficient power (80%) for the main effect of wheel-running exercise on [18F]Fallypride BP to be detected at an alpha-level of 5%. Finally, autoradiography studies, performed on the same mice with [18F]Fallypride, will strengthen our in vivo results. [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 detailThe use of PRISMA statement improves the reporting quality of meta-analyses published in the field of psychology
Leclercq, Victoria ULiege; Beaudart, Charlotte ULiege; Ajamieh, Sara ULiege et al

in Value in Health Regional Issues (2018, October), 21

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See detailEvidence for a long-term protection of wheel-running exercise against cocaine psychomotor sensitization in adolescent but not in adult mice
Lespine, Louis-Ferdinand ULiege; Tirelli, Ezio ULiege

in Behavioural Brain Research (2018), 349

Rodents housed with a running wheel can exhibit attenuated cocaine seeking and cocaine-induced psychomotor activation. However, the longevity of such a protection and the influence of the developmental ... [more ▼]

Rodents housed with a running wheel can exhibit attenuated cocaine seeking and cocaine-induced psychomotor activation. However, the longevity of such a protection and the influence of the developmental stage during which exercise is displayed received little attention. Here, females and males C57BL/6J mice, aged 28 (adolescents) or 77 (adults) days were housed with (n = 56) or without (n = 28) a running wheel. After 3 weeks in these conditions, half of the exercised mice were deprived of their wheel (n = 28) whereas the other half and the sedentary mice were kept in their respective environments. After 3 additional weeks, mice were tested for initiation of psychomotor sensitization to 9 once-daily intraperitoneal injections of 8 mg/kg cocaine (following 2 drug-free sessions). The expression of sensitization was assessed on a single session 30 days after the last cocaine injection. Continuously exercised mice (wheel throughout experimentation) were less responsive to the initiation and the expression of cocaine effects, regardless of the gender and the developmental period during which exercise was introduced. A 3-week regimen of wheel-running exercise during adolescence (from 28 to 50 days of age) attenuated in later life the initiation and the expression of sensitization in females and its expression in males. In contrast, females and males previously exercised as adults (from 77 to 99 days of age) and their corresponding sedentary counterparts exhibited indiscernible levels of initiation and expression of sensitization. These results suggest that early-life period such as adolescence may be particularly sensitive to the long-term protection of exercise against cocaine vulnerability. [less ▲]

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See detailDecrease in SV2A expression in the hippocampus involves changes in cognition and anxiety-like features.
Serrano Navacerrada, Maria Elisa ULiege; Bartholomé, Odile ULiege; Van Den Ackerveken, Priscilla ULiege et al

Poster (2018, July)

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose link with the epilepsy has been reported in multiples articles. However, the behavioral consequences of the decrease in its ... [more ▼]

The Synaptic Vesicle Protein 2A (SV2A) is a transmembrane protein whose link with the epilepsy has been reported in multiples articles. However, the behavioral consequences of the decrease in its expression remain still unclear. The purpose of our research is to better understand the role of this protein through the evaluation of cKO (Grik4 +/-, SV2A lox/lox) mice of both sexes, which present a specific decrease in the hippocampus. After a first evaluation of the SV2A levels in the hippocampus with the in vitro [18F]UCB-H autoradiography, differences in brain metabolism were assessed with [18F]FDG in mPET and ex vivo autoradiography. Finally, the phenotype of cKO mice was analyzed with a behavioral test battery. Our results showed a strong reduction of SV2A expression in the whole hippocampus of cKO mice, with regard to the WT mice, not accompanied by statistically significant differences in brain metabolism between groups, either in vivo or ex vivo. No statistically significant differences were found in spontaneous locomotor activity or fear-linked memory. However, cKO males showed significant more anxiety than WT (less percent of entries in open arms) and females presented spatial memory deficits measured in the Barnes Maze (less time spend in quadrant during the test). These results could explain the comorbidity between anxiety, memory impairment and epilepsy present both in animal models and in humans, suggesting an important role of SV2A in the symptomatology of other neurodegenerative diseases, such as the Alzheimer disease, or in anxiety-related pathologies. [less ▲]

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See detailLa souris, le patient, et le faux expert. Décryptage d'une mystification.
Bakker, Julie ULiege; Balthazart, Jacques ULiege; Baron, Frédéric ULiege et al

Article for general public (2018)

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les ... [more ▼]

La recherche sur animaux est actuellement encadrée de façon stricte en Wallonie comme dans toute l'Union Européenne (voir l'article de Marc Vandenheede publié dans le Vif). Cette législation et les contrôles qui y sont associés induisent de nombreuses contraintes pratiques, des charges administratives et des coûts financiers importants que les chercheurs seraient certainement heureux d'éviter s'il existait une alternative à l'expérimentation animale. [less ▲]

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See detailIncreased hippocampal volume in exercising mice: comparison of control conditions with in vivo voxel based morphometry
Becker, Guillaume ULiege; Lespine, Louis-Ferdinand ULiege; Bahri, Mohamed Ali ULiege et al

Poster (2018, March)

Introduction Both human and animal studies have shown that physical exercise (primarily aerobic exercise) may have facilitating effects on brain plasticity and cognition. In rodents, improvements of ... [more ▼]

Introduction Both human and animal studies have shown that physical exercise (primarily aerobic exercise) may have facilitating effects on brain plasticity and cognition. In rodents, improvements of various forms of learning and memory induced by wheel-running have been associated with numerous neuroplastic changes such as increased hippocampal neurogenesis. A few studies, using magnetic resonance imaging (MRI), consistently reported hippocampal volumetric increase relative to non-exercising mice. However, the control group is commonly limited either to a locked wheel or no wheel. Methods In the present study, we intended to test whether 6 weeks of voluntary wheel-running exercise during adulthood induced a detectable volumetric change in mice brain in comparison to non-exercised control mice housed either with a locked wheel or without such wheel. 54 C57Bl6 males were randomly assigned to one of the three groups and individually housed for 6 weeks before imaging session. MRI (Agilent 9.4T) acquisition consisted in 3D T2 volume sequence (voxel size: 0.21 mm isotropic) using a dedicated surface coil receiver. We used Dartel soware for the preprocessing of the data, and the Voxel Based Morphometry was done with SPM mouse toolbox (F test, threshold p < .001 uncor). A small volume correction was applied to limit the analysis to the hippocampus. Results/Discussion VBM analysis shows significant clusters with increased grey matter volume in the hippocampus (cluster sizes 1531 and 3460, p < .001) when we compare the wheel vs locked wheel groups. Regarding the wheel vs no wheel comparison, significant clusters were observed in the hippocampus (cluster sizes 955 and 238, p < .001). Interestingly, no dierences were found when we compare the two control groups (locked wheel vs no wheel). Conclusions In this study, we replicate previous studies depicting an increased hippocampal volume under physical exercise in mice using VBM. Moreover, we certified here that attempting to study the impact of physical exercise on brain volume, control groups with a locked wheel or no wheel are equivalent. [less ▲]

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See detailFunctional correlates of the protective effects of free wheel-running against cocaine psychomotor sensitization on dopamine D2 receptors: a [18F]Fallypride microPET study.
Becker, Guillaume ULiege; Lespine, Louis-Ferdinand ULiege; Bahri, Mohamed Ali ULiege et al

Conference (2017, April 05)

Preclinical studies suggest that free access to a running wheel can attenuate the behavioural responsiveness to addictive drugs in rodents. Regarding the behavioural responsiveness to drugs, psychomotor ... [more ▼]

Preclinical studies suggest that free access to a running wheel can attenuate the behavioural responsiveness to addictive drugs in rodents. Regarding the behavioural responsiveness to drugs, psychomotor sensitization has an integral role in the process of drug addiction in craving and relapse (Steketee and Kalivas, 2011). Free wheel-running was recently shown to be efficacious at preventing the initiation or the long-term expression of psychomotor sensitization to cocaine in mice or rats (Diaz et al., 2013; Geuzaine and Tirelli, 2014). In the present study, we investigated the neuro-functional correlates of the protection against psychomotor sensitization to cocaine afforded by free wheel-running on dopaminergic neurotransmission, using microPET imaging with [18F]Fallypride, a Dopamine 2 receptor (D2R) antagonist. We used a total of 32 female C57BL/6J mice. At 28 days of age, the mice were randomly assigned to on of the two experimental housing conditions, defined by the presence or the absence of a running wheel in the cage (pre-testing period: 6 weeks). Since mice from the two types of housing received either saline or cocaine (8 mg/kg, i.p.) during testing (9 days), a basic 2*2 factorial design was generated (two-way ANOVA). The whole experimentation lasted 85 days, included the 42-days pre-testing period and the 3 weeks (housing condition, no injection) between the testing and the long-term expression of sensitization (LTES). All mice underwent a microPET (Focus 120, Siemens) the day after the LTES. The microPET protocol consisted of a 60 min. dynamic acquisition after the injection of 10 MBq of [18F]Fallypride in the tail vein. We observe a strong attenuating effect of exercise on the expression of sensitization to cocaine (Effect Size = 2.66 at p < .001 one-tailed, N.B: Effect Size is the mean difference in standard deviation units). Regarding the microPET outcomes ([18F]Fallypride Binding Potential, BP), we have a significant increase of the [18F]Fallypride BP for the cocaine-treated mice, compared to the saline-injected mice (Effect Size = 0.78 at p = .02 one-tailed). We observe a decrease tendency of the [18F]Fallypride BP in the exercise condition compared to the sedentary condition (ES = 0.48 at p = .09 one-tailed). These findings indicate that LTES is associated with an increase of the [18F]Fallypride BP in the mouse striatum, probably reflecting an increase in postsynaptic D2R density in this region. Besides that, the protecting effect of free running on psychomotor sensitization goes together with a decrease in D2R density in the striatum of exercised mice. Those data will be augmented with identical sub-experiment. All data will be pooled together to reach a total number of 64 mice (n = 16 per group). [less ▲]

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See detailWheel-running exercise during adolescence does not substantially affect cocaine conditioned place preference in male C57BL/6J mice
Lespine, Louis-Ferdinand ULiege; Tirelli, Ezio ULiege

Poster (2017)

Epidemiological studies suggest that physical exercise could have preventive properties against drugs of abuse vulnerability. Animal research showed that rats or mice housed with a running wheel (a model ... [more ▼]

Epidemiological studies suggest that physical exercise could have preventive properties against drugs of abuse vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of aerobic exercise) can exhibit attenuated drug self-administration or drug-induced psychomotor hyperactivity in comparison with their sedentary counterparts. However, the few experiments using conditioned place preference (CPP) are conflicting (positive, negative or null effects of exercise). Aspects or deficiencies of the methods used in some studies, in particular the low sample size (median n=8), the absence of a baseline pre-conditioning session or a control group in the design or (when present) in the data analyses, make the whole picture of results difficult to understand, a situation which warrants further studies, possibly of a better quality than the previous ones. Objectives. 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. Method. Male C57BL/6J mice were individually housed either with (n=32) or without (n=32) a running wheel from 35 days of age. Behavioral testing begun 3 weeks after such housing, all animals being first tested under saline for their baseline preference (white or black compartments). Then, mice underwent 10 once-daily conditioning sessions receiving peritoneal injections of 10 mg/kg cocaine and saline on alternate days (n=16). The white compartment (always non-preferred) was systematically associated to cocaine effects. Control mice received saline every day (n=16). One and 21 days after the last conditioning session, mice were tested for place preference under saline. CPP scores were analyzed with a priori single (cocaine vs saline) and crossed contrasts (testing the housing-by-drug interaction). Each contrast (t-test) incorporated the mean-square error (MSE) provided by a preliminary two-way fixed-model 2x2 ANOVA incorporating the housing condition (2 levels) and the drug treatment (2 levels) as between-group factors and time of testing as a blocking factor (8 levels). Estimates of effect sizes were provided by Cohen’s d calculated from ts and degree of freedom. Results. The two groups exhibited significant well-marked cocaine-induced CPP in both 1-day (d = 1.38 and d = 1.11 at ps < .001 one-tailed in exercised and sedentary mice) and 21-day post-conditioning tests (d = 1.09 and d = 1.15 at ps < .001 one-tailed in exercised and sedentary mice). The (small) effects underlying interaction between housing and the drug treatment were not significant for 1-day (d = 0.19 at p = .48 two-tailed; 95% CI -0.35 to 0.73) or 21-day post-conditioning tests (d = 0.05 at p = .87 two-tailed; 95% CI -0.49 to 0.59). Conclusion. If physical exercise in rodents “truly” impacts CPP induced by drugs of abuse under comparable experimental parameters - as suggested by some studies (either positively or negatively) -, our results indicate that the size of such effects may be quite small, an information rarely reported in the literature. [less ▲]

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See detailLong-term effects of exercise during youth or adulthood on cocaine reactivity in mice: qualitative developmental differences
Lespine, Louis-Ferdinand ULiege; Tirelli, Ezio ULiege

Conference (2017)

Epidemiological studies suggest that physical exercise could have preventive properties on drugs vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of physical ... [more ▼]

Epidemiological studies suggest that physical exercise could have preventive properties on drugs vulnerability. Animal research showed that rats or mice housed with a running wheel (a model of physical exercise) can exhibit attenuated drug seeking and drug-induced psychomotor hyperactivity in comparison with their sedentary counterparts. Objectives: the aim was to evaluate the longevity of the protective effects of exercise on cocaine vulnerability and the influence of the developmental stage during which exercise is applied (in 4 experiments). Method: females and males C57BL/6J mice, aged 28 (youth) or 77 days (adults) were housed with (n=56) or without (n=28) a running wheel. After 3 weeks, half of the exercised mice (n=28) were deprived of their wheel (3 housing conditions/experiment). Three weeks later, mice were tested for sensitization to the psychomotor-activating effects of 8 mg/kg cocaine over 9 once-daily sessions (controls: saline solution). Mice were also tested 30 days later for their long-term expression of sensitization. Results: continuous wheel-running housing reduced cocaine responsiveness in both females and males regardless of the age on which exercise was introduced. Exercise performed exclusively in youth, but not over adulthood, reduced durably cocaine responsiveness, particularly in females. Conclusion: the likelihood of the long-term protection of exercise against cocaine responsiveness may depend on the age of exercise application and the gender. [less ▲]

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See detailBehavioural phenotyping of SV2A lox/lox mice: Motor and anxiety-like features
Serrano Navacerrada, Maria Elisa ULiege; Bartholomé, Odile ULiege; Van Den Ackerveken, Priscilla ULiege et al

Poster (2017)

Background: Epilepsy is one of the most common neurological disorders (Alexopoulos, 2004). Current anti-epileptic drugs, such as Levetiracetam (Keppra®) or Brivaracetam, mainly target the trans-membrane ... [more ▼]

Background: Epilepsy is one of the most common neurological disorders (Alexopoulos, 2004). Current anti-epileptic drugs, such as Levetiracetam (Keppra®) or Brivaracetam, mainly target the trans-membrane Synaptic Vesicle Protein 2A (Hamann et al., 2008). Studies on homozygous SV2A KO mice phenotype, prove the mice to suffer severe seizures and die within 3 weeks (Crowder et al., 1999), establishing a link between this protein and the epilepsy. In 2009, the availability of heterozygous SV2A (+/-) mice as research tool enabled shedding light on the role of protein SV2A, revealing no motor differences but anxiety-like features in these mice compared with the WT (Lamberty et al., 2009), and a pro-epileptic phenotype (Crowder et al., 1999; Kaminski et al., 2008). Recently, a floxed SV2A mouse model has been produced with the Cre/loxP recombination system, this model allows invalidating the protein in CA3 hippocampal region, not followed by epileptic seizures (Menten-Dedoyart et al., 2016). Objectives: Perform a first behavioural phenotyping of SV2A lox/lox mice. Methodology: Two experiments were conducted in parallel to evaluate the effect of 3 different genotypes in the phenotype: WT (Grik4-/-, SV2A lox/lox), HZ (Grik4 +/-, SV2A lox/+) and cKO (Grik4 +/-, SV2A lox/lox) in male (n = 42) and female (n = 33) separately . Mice were housed individually along the experiment, with standard food and water ad libitum. After an acclimatization period of 2 weeks, anxiety-like features as well as exploration abilities were evaluated in an elevated plus-maze (EPM) single session of 5 minutes). 3 days later, spontaneous locomotor activity and habituation to the environment were measured during 1 hour, 3 consecutive days, in the activity chambers (ACT). Results: One-way ANOVA in EPM data presented no significant differences between groups, either in males or in females. A significant difference was found, between time spent in close arms vs open arms (p<0.01; η2p = 0.738 males; η2p = 0.805 females). Mixed between-within subjects ANOVA in ACT reflected no significant differences between groups in both sexes, regarding spontaneous locomotor activity and acclimatization to the activity chamber (p>0.05). Statistical significant differences were found between the 3 days (p<0.01; η2p = 0.716 males; η2p = 0.663 females). Conclusion: Results indicate that a decrease in the hippocampal expresion of SV2A protein does not lead to major behavioral changes. Regarding locomotor activity, the results found in heterozygous SV2A (+/-) mice are in line with (Lamberty et al., 2009), however, our mice did not present anxiety-like features, being necessary a global decrease in brain SV2A levels and not only a partial loss in a restricted region of the brain. Further analyses increasing the number of mice per group, will allow us to intensify our power value from 50-60% (females-males) up to 80%, with large effect size and a signification of p<0.05. An additional test to evaluate the spatial memory may help us better understand the effect a specific reduction in SV2A hippocampal expression has on the phenotype of mice. [less ▲]

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See detailStudy Protocol: Effect of prenatal wheel-running exercise (before and during gestation) on cocaine psychomotor sensitization expressed in the offspring in periadolescent females and males C57BL/6J mice
Lespine, Louis-Ferdinand ULiege; Plenevaux, Alain ULiege; Tirelli, Ezio ULiege

E-print/Working paper (2017)

The present study principally aims at determining to which extent prenatal exercise (before and during gestation) could affect the initiation (establishment) and the expression of psychomotor ... [more ▼]

The present study principally aims at determining to which extent prenatal exercise (before and during gestation) could affect the initiation (establishment) and the expression of psychomotor sensitization induced by a representative dose of cocaine in young female and male mice. More specifically, we will assess cocaine-induced acute psychomotor-activating effects, psychomotor sensitization developing over 9 daily sessions (daily peritoneal injections of cocaine or saline) and the long-term expression of the sensitized response (30 days after the last sensitizing injection) in C57BL/6J mice born from mothers housed with or without a running wheel before and during gestation. Based on literature and on our prior results, the mice born from exercised mothers are expected to show significantly reduced levels of cocaine responsiveness in comparison with the control mice (born from unexercised mothers). [less ▲]

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See detailDifferential effects of context on psychomotor sensitization to ethanol and cocaine
Didone, Vincent ULiege; Quoilin, Caroline; Dieupart, Julie et al

in Behavioural Pharmacology (2016), 27(2 & 3), 173-181

Repeated drug injections lead to sensitization of their stimulant effects in mice, a phenomenon sometimes referred to as drug psychomotor sensitization. Previous studies showed that sensitization to ... [more ▼]

Repeated drug injections lead to sensitization of their stimulant effects in mice, a phenomenon sometimes referred to as drug psychomotor sensitization. Previous studies showed that sensitization to cocaine is context dependent as its expression is reduced in an environment that was not paired with cocaine administration. In contrast, the effects of the test context on ethanol sensitization remain unclear. In the present study, female OF1 mice were repeatedly injected with 1.5 g/kg ethanol to test for both the effects of context novelty/familiarity and association on ethanol sensitization. A first group of mice was extensively pre-exposed to the test context before ethanol sensitization and ethanol injections were paired with the test context (familiar and paired group). A second group was not pre-exposed to the test context, but ethanol injections were paired with the test context (nonfamiliar and paired group). Finally, a third group of mice was not pre-exposed to the test context and ethanol was repeatedly injected in the home cage (unpaired group). Control groups were similarly exposed to the test context, but were injected with saline. In a second experiment, cocaine was used as a positive control. The same behavioral procedure was used, except that mice were injected with 10 mg/kg cocaine instead of ethanol. The results show a differential involvement of the test context in the sensitization to ethanol and cocaine. Cocaine sensitization is strongly context dependent and is not expressed in the unpaired group. In contrast, the expression of ethanol sensitization is independent of the context in which it was administered, but is strongly affected by the relative novelty/familiarity of the environment. Extensive pre-exposure to the test context prevented the expression of ethanol sensitization. One possible explanation is that expression of ethanol sensitization requires an arousing environment. [less ▲]

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See detailThe protective effects of free wheel-running against cocaine psychomotor sensitization persist after exercise cessation in C57BL/6J mice
Lespine, Louis-Ferdinand ULiege; Tirelli, Ezio ULiege

in Neuroscience (2015), 310

Previous literature suggests that free access to a running wheel can attenuate the behavioral responsiveness to addictive drugs in rodents. In a few studies, wheel-running cessation accentuated drug ... [more ▼]

Previous literature suggests that free access to a running wheel can attenuate the behavioral responsiveness to addictive drugs in rodents. In a few studies, wheel-running cessation accentuated drug responsiveness. Here, we tested whether free wheel-running cessation is followed by (1) an accentuation or (2) an attenuation of cocaine psychomotor sensitization, knowing that no cessation of (continuous) wheel-running is associated with an attenuation of cocaine responsiveness. Male C57BL/6J mice, aged 35 days, were housed singly either with (exercising mice) or without (non-exercising mice) a running wheel. At the end of a period of 36 days, half of the exercising mice were deprived of their wheel whereas the other half of exercising mice kept their wheel until the end of experimentation (which lasted 85 days). The non-exercising mice were housed without wheel throughout experimentation. Testing took place 3 days after exercise cessation. After 2 once-daily drug-free test sessions, mice were tested for initiation of psychomotor sensitization over 13 once-daily injections of 8 mg/kg cocaine. Post-sensitization conditioned activation (saline challenge) and long-term expression of sensitization were assessed 2 or 30 days after the last sensitizing injection (same treatments as for initiation of sensitization), respectively. Exercising mice and mice undergoing wheel-running cessation exhibited comparable degrees of attenuation of all cocaine effects in comparison with the continuously non-exercising mice, which showed the greatest effects. Thus, the efficaciousness of wheel-running at attenuating cocaine sensitization not only resisted to exercise cessation but also was unambiguously persistent (an important effect rarely reported in previous literature). [less ▲]

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See detailExploration of volumetric cerebral changes, with de micro-MRi, due to psychomotor exercise in mice
Moës, Florian ULiege; Plenevaux, Alain ULiege; Becker, Guillaume ULiege et al

Poster (2015, January 27)

It's well know that exercise is good for health .In addition exercise has postive effects on cognition ,neurodegenerative disease and on mood. Some studies show that exercise has effect on brain so the ... [more ▼]

It's well know that exercise is good for health .In addition exercise has postive effects on cognition ,neurodegenerative disease and on mood. Some studies show that exercise has effect on brain so the aim of this study is to see if there are volumetric changes due to exercise or not. [less ▲]

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See detailEffects of α-synuclein levels on cerebral synaptic function: Validation of a novel PET radioligand for the early diagnosis of Parkinson’s disease
Tarragon Cros, Ernesto ULiege; Ferrara, André ULiege; Tirelli, Ezio ULiege et al

Poster (2015, January 27)

Background In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells ... [more ▼]

Background In Parkinson’s disease, converging evidence supports a pathogenic role for excessive α–synuclein accumulation in synaptic terminals that may propagate back to the soma of vulnerable nerve cells such as neurons in the substantia nigra pars compacta. The resulting loss of dopaminergic terminals in the striatum can be demonstrated in vivo using 18F-Dopa-PET (positron emission tomography). However, there’s currently no validated biomarker of the progressive synaptic dysfunction in other vulnerable areas such as the cerebral cortex. Goal In this longitudinal study, we will test the hypothesis that the loss of synaptic terminals in a mouse model of excessive α–synuclein accumulation can be demonstrated in vivo before the occurrence of behavioural disturbances using 18F-UCB-H, a new PET biomarker developed at CRC. We will also test if this new imaging modality is sensitive enough to study the effect of a disease modifying therapy such as chronic physical exercise. Methods We will use microPET for the in vivo quantification of 18F-UCB-H brain uptake in 16 wild type animals and 16 transgenic (Tg) mice overexpressing human α–syn under the mThy1 promotor every 2 months. Data will be validated against post-mortem analyses after the last PET study. Predictions We predict decreased tracer uptake over time in the basal ganglia and cerebral cortex in Tg mice as compared with WT animals. Also, we predict a relationship between 18F-UCB-H uptake levels in basal ganglia and cerebral cortex and progressive alterations in both motor and cognitive functions, respectively. Further, we also expect that chronic exercise will slow down both motor and cognitive disturbances, as well as the rate of 18F-UCB-H brain uptake decreases. Conclusion If 18F-UCB-H PET proves to be a valid biomarker for the early detection of α–synuclein accumulation in the pre-clinical model of PD, the methods will tested on human clinical populations. [less ▲]

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See detailHigher long-lasting ethanol sensitization after adolescent ethanol exposure in mice
Quoilin, Caroline; Didone, Vincent ULiege; Tirelli, Ezio ULiege et al

in Psychopharmacology (2014), 231

Rationale. Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is ... [more ▼]

Rationale. Due to their maturing brain, adolescents are suggested to be more vulnerable to the long-term consequences of chronic alcohol use. Increased sensitization to the stimulant effects of ethanol is a possible consequence of ethanol exposure during adolescence. Objectives. The aim of this study was to characterize the long-term alterations in the stimulant effects of ethanol and in the rate of ethanol sensitization in mice pre-exposed to ethanol during adolescence in comparison to mice pre-exposed to ethanol in adulthood. Methods. Adolescent and adult female SWISS mice were injected with saline or ethanol (2.5 or 4 g/kg) during 14 consecutive days. After a three weeks period of ethanol abstinence, mice were tested as adults before and after a second exposure to daily repeated ethanol injections. Results. All mice pre-exposed to ethanol as adults or adolescents showed higher stimulant effects when re-exposed to ethanol three weeks later. However, this enhanced sensitivity to the stimulant effects of ethanol was of significantly higher magnitude in mice repeatedly injected with high ethanol doses (4g/kg) during adolescence. Furthermore, the increased expression of ethanol stimulant effects in these mice was maintained even after a second procedure of ethanol sensitization. Conclusions. Adolescence is a critical period for the development of a sensitization to ethanol stimulant properties providing that high intermittent ethanol doses are administered. These results might contribute to explain the relationship between age at first alcohol use and risks of later alcohol problems and highlight the dangers of repeated consumption of high alcohol amounts in young adolescents. [less ▲]

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