Biology subjects

Tirelli, E.

Publications and source records attributed to Tirelli, E..

6 recordsLinked to original sources

bioRxiv2020

Multi- and transgenerational disruption of maternal behavior and female puberty by Endocrine Disrupting Chemical (EDC) mixture exposure

Female reproductive development and maternal behavior are two intertwined phenotypes centrally controlled by the hypothalamus. Endocrine disrupting chemicals (EDC) can alter these processes especially when animals are exposed during development. We propose the concept that developmental exposure to a low environmentally relevant dose of EDC mixture induces a transgenerational alteration of female rat pubertal timing and ovarian physiology throughout epigenetic reprograming of hypothalamic Kiss1, Esr1 and Oxt1 loci. Such exposure also caused a multigenerational reduction of maternal behavior induced by the loss in hypothalamic dopaminergic signaling. Our results identify the hypothalamic Polycomb Group of epigenetic repressors as actors of this mechanism of transgenerational reproductive disruption. Using a cross-fostering approach, we identified that while the reduction in maternal phenotype was normalized in EDC exposed pups raised by unexposed dams, no reversal of the pubertal phenotype was achieved, suggesting a germline transmission of the reproductive phenotype.

neuroscience↗

bioRxiv2019

Neuro-functional correlates of protective effects of wheel-running exercise against cocaine locomotor sensitization in mice: a fallypride microPET study

Wheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioral markers of vulnerability to addictive properties of various drugs of abuse including cocaine. However, neurobiological mechanisms underpinning this protective effect are far from being fully characterized and understood. 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 microPET imaging session with [18F]fallypride radiotracer (dopamine 2/3 receptor (D2/3R) 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 ({eta}2p = 0.262). Additionally, we found that chronic administrations of cocaine was associated with a clear-cut increase of [18F]fallypride binding potential in mouse striatum ({eta}2p = 0.170), presumably reflecting an increase in postsynaptic D2/3R density in this region. Finally, we found evidence that wheel-running exercise was associated with a moderate decrease in D2/3R density in striatum ({eta}2p = 0.075), a mechanism that might contribute to protective properties of such form of exercise against drugs of abuse vulnerability.

neuroscience↗

bioRxiv2019

Long-term exposure to daily ethanol injections in DBA2/J and Swiss mice: Lessons for the interpretation of ethanol sensitization

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.\n\nSwiss and DBA2/j 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.\n\nThe 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. 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.

neuroscience↗

bioRxiv2018

Wheel-running exercise before and during gestation against acute and sensitized cocaine psychomotor-activation in offspring

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/6J 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 = .02), whereas there was no evidence for such a difference in males (d = 0.34, p = .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 (Cohens ds varying from -0.23 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.

neuroscience↗

bioRxiv2018

Wheel-running exercise during adolescence may not convincingly impact cocaine conditioned place preference in male C57BL/6J mice

Wheel-running in rodents can mitigate addiction-related effects of drugs of abuse like cocaine. However, experiments using conditioned place preference (CPP) are conflicting, warranting further studies. Our purpose was to test whether wheel-running during adolescence could impact the formation and long-term retention of CPP to cocaine in mice. Male C57BL/6J 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 ({eta}{superscript 2}p < 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.

neuroscience↗

bioRxiv2017

Evidence for a long-term protection of wheel-running exercise against cocaine psychomotor sensitization in adolescent but not in young adult mice

Rodents housed with a running wheel can exhibit attenuated cocaine seeking and cocaine-induced psychomotor activation. However, the longevity of the exercise anti-drug 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 (young 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 (no wheel) were kept in their respective environments throughout experimentation. 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 test sessions). The expression of sensitization was assessed on a single test session 30 days after the last sensitizing 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. Wheel-running during adolescence attenuated in later life the initiation and the expression of sensitization in females and only its expression in males. In adult females and males, previously-exercised and sedentary mice exhibited indiscernible levels of initiation and expression of sensitization. Thus, the likelihood of the long-term protection of exercise against cocaine vulnerability may depend not only on the gender but also and especially on the period of life in which exercise took place.

neuroscience↗