Biology subjects

Dugast, E.

Publications and source records attributed to Dugast, E..

4 recordsLinked to original sources

bioRxiv2025

Environmental enrichment selectively restores brain metabolic activity during cocaine abstinence

BackgroundEnvironmental enrichment (EE) is a promising strategy to promote recovery from addiction, but its neurobiological mechanisms remain poorly understood. This study investigates how exposure to EE during abstinence dynamically affects brain neuroadaptations induced by voluntary intake of cocaine. MethodsUsing longitudinal 18FDG microPET imaging, we examined brain metabolic activity in rats following extended access cocaine self-administration. After establishing escalation of cocaine intake, rats were housed in either enriched or standard environments during a four-week abstinence period. Brain metabolic activity was assessed after one and four weeks of abstinence. ResultsCocaine self-administration produced widespread decreases in cortical metabolic activity, particularly in regions involved in executive function (orbitofrontal cortex, anterior cingulate) and interoception (insula), while increasing activity in emotional and motivational circuits (nucleus accumbens, amygdala, mesencephalon). EE selectively normalized these alterations through temporally distinct mechanisms: rapidly restoring nucleus accumbens and amygdala function while gradually affecting prefrontal cortical activity. After four weeks, rats housed in enriched environments showed significantly normalized metabolic activity in the orbitofrontal cortex and dorsolateral striatum compared to those in standard housing, with persistent changes in anterior cingulate cortex and ventral posterior hippocampus. ConclusionsOur findings reveal circuit-specific and temporally distinct effects of environmental enrichment on cocaine-induced brain alterations. These insights could inform the development of more targeted therapeutic approaches for addiction recovery.

neuroscience↗

bioRxiv2023

Effects of high fat and sugar diet on motivation for food and resistance to punishment in rats: role of sex and age of exposure

Exposure to food rich in fat and sugar (High Fat and Sugar Diet, HFSD) is believed to induce behavioral and neurobiological changes that would produce addiction-like behavior and increase the risks of obesity and overweight. Studies in rodents have led to conflicting results suggesting that several factors such as sex and age of exposure contribute to the development of maladaptive behavior towards food. In addition, it is not clear whether the effects of exposure to HFSD persist after its discontinuation which would indicate long-term risk to develop addiction-like behavior. In this study, we investigated the persistent effects of an intermittent 8-week exposure to HFSD in male and female rats as a function of age of exposure (adult and adolescent). We found that intermittent exposure to HFSD did not alter body weight, but it affected consumption of standard food during the time of exposure in all groups. In addition, in adults, HFSD produced a decrease in the initial baseline responding in FR1 schedules that persisted for 4 weeks in males but not in female rats. However, we found that exposure to HFSD did not affect resistance to punishment measured by progressive shock strength (PSS) break points or motivation for food measured by progressive-ratio break points regardless of sex or age of exposure. Altogether, these results do not provide support to the hypothesis that intermittent exposure to HFSD produce persistent increases in the vulnerability to develop addiction-like behaviors towards palatable food.

neuroscience↗

bioRxiv2023

Sex-dependent effects of stress on insular cortex-to-nucleus accumbens synaptic plasticity

Stress is an important risk factor for the development of psychiatric disorders and men and women tend to react differently to stress. Sex differences are also observed in many stress-related psychiatric disorders such as depression, anxiety disorders or addiction. Therefore, identifying specific neuroadaptations induced by stress, in males and females, is a necessary step to the understanding of stress-related sex dimorphism in these disorders. Here, we tested the hypotheses that acute stress could affect plasticity in the anterior insular cortex (aIC)-nucleus accumbens core (NAcC) pathway, two structures involved in the stress response, in a sex-dependent manner. Using in vivo extracellular recordings in anesthetized rats, we show that synaptic plasticity in the aIC-NAcC pathway is different between male and female rats. Whereas in males, long-term potentiation and long-term depression were equally induced, in females, there was mostly a long-term potentiation induced. Moreover, stress affected synaptic plasticity in the aIC-NAcC differently in male and female rats. In males, stress induced a loss of long-term-depression that lasted for at least 24h, whereas in females, stress induced less neurons displaying LTP, which did not last. These results demonstrate that integration of aIC information to NAcC is different between males and females. This study provides mechanistic support for differential reactivity to stress between males and females that may relate to stress-related psychiatric disorders and sex dimorphism in these disorders.

neuroscience↗

bioRxiv2023

Cognitive effort increases the intensity of rewards

An important body of literature suggests that exerting intense cognitive effort causes mental fatigue and can lead to unhealthy behaviors such as indulging in high-calorie food and taking drugs. Whereas this effect has been mostly explained in terms of weakening cognitive control, cognitive effort may also bias behavioral choices by amplifying the hedonic and emotional impact of rewards. We report parallel findings with animals and humans supporting this hypothesis. In rats, exerting cognitive effort immediately before access to cocaine self-administration significantly increased drug intake. In addition, exerting cognitive effort increased the psychostimulant effect of cocaine. The effects of cognitive effort on addiction-related behaviors were eliminated and even reversed when animals could rest in their home-cage for 2-4h before access to cocaine self-administration. Among humans, we found that expending cognitive effort increased consumption of tasty (but unhealthy) food by increasing the hedonic enjoyment of consuming the food. In addition, the effects were specific for emotionally relevant stimuli (i.e., food rewards) and did not generalize to judgment about neutral objects. Altogether these data suggest that intense cognitive effort can increase the perceived intensity of rewards and lead to their overconsumption. This effect may contribute to bad decision making induced by excessive cognitive effort and make people more vulnerable to indulge in unhealthy behaviors such as use of addictive drugs. Significance StatementPeople dieting or recovering from addiction frequently report that relapses occur during periods of stress and mental fatigue. Multiple processes may contribute to this, including beliefs about the stress-reducing effects of drugs, beliefs about ones inability to continue resisting, and lack of energy needed to sustain resistance. Here, we suggest an additional possible process: during a state of mental fatigue, rewards become all the more satisfying, thereby also increasing subsequent desire for them. We report two lines of experiments, one with rats and one with human participants, to show that intense cognitive effort leads to increased enjoyment of rewards and hence increased consumption.

neuroscience↗