Search bioRxiv⌕ Search

Biology subjects

Lardeux, V.

Publications and source records attributed to Lardeux, V..

5 recordsLinked to original sources

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↗

Delay of punishment highlights differential vulnerability to developing addiction-like behavior toward sweet food

Resistance to punishment is commonly used as a measure of compulsive behavior in addiction-related processes. We recently developed a progressive shock strength (PSS) procedure in which individual rats can titrate the amount of punishment that they are willing to tolerate to obtain food rewards. Here, we investigated the effects of a range of delays (0-12 sec) on resistance to punishment measured by PSS break points. As expected from delay discounting principles, we found that delayed shock was less effective as a punisher, as revealed by higher PSS breakpoints. However, this discounting effect was not equally distributed in the population of rats, and the introduction of a delay highlighted the existence of two populations: rats that were sensitive to immediate punishment were also weakly sensitive to delay, whereas rats that were resistant to immediate punishment showed strong temporal discounting of delayed punishment. Importantly, shock-sensitive rats suppressed responding even in non-punishment sessions, and they differed from shock-resistant rats in anxiety- like behavior but not in sensitivity to pain. These results show that manipulation of temporal contingencies of punishment in the PSS procedure provides a valuable tool to identify individuals with a double vulnerability to addiction: low sensitivity to aversion and excessive discounting of negative future consequences. Conversely, the shock-sensitive population may provide a model of humans who are vulnerable to opportunity loss due to excessive anxiety.

animal behavior and cognition↗

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↗

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↗

A self-adjusting, progressive shock magnitude procedure to investigate resistance to punishment: characterization in male and female rats

Indifference to harmful consequences is one of the main characteristics of compulsive behaviors and addiction. Animal models that provide a rapid and effective measure of resistance to punishment could be critical for the investigation of mechanisms underlying these maladaptive behaviors. Here, analogous to the progressive ratio (PR) procedure widely used to evaluate appetitive motivation as the response requirement is increased, we developed a self-adjusting, progressive shock strength (PSS) procedure. The PSS provides, within a single session, a break point that quantifies the propensity to work for a reward in spite of receiving electric footshock that progressively increases in duration. In both male and female rats, the PSS break point was sensitive to 1) hunger; and 2) changes in the qualitative, but not quantitative, incentive value of the reward. In systematic comparisons between PSS and PR procedures in the same rats, we found that both measures are sensitive to manipulations of motivational states, but they are not intercorrelated, suggesting that they measure overlapping but partially distinct processes. Importantly, the PSS procedure represents a refinement in the 3Rs principles of animal research because animals can control the strength of shock that they are willing to tolerate. This self-adjusting PSS procedure may represent a useful tool to investigate mechanisms underlying maladaptive behavior that persists in certain individuals despite harmful consequences.

animal behavior and cognition↗