Biology subjects

Solinas, M.

Publications and source records attributed to Solinas, M..

9 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

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↗

bioRxiv2023

Cue-Induced Drug Seeking and Its Association with Craving and Dependence in Cigarette Smokers

IntroductionIncreased salience of drug-related cues over non-drug reinforcers can drive drug use and contribute to tobacco use disorder (TUD). An important scientific and clinical goal is to effectively measure this elevated drug-seeking behavior in TUD. However, most TUD assessments rely on self-reported cravings and cigarette consumption, not providing an objective measure of the impact of drug-cues on biasing behavior towards drugs. The probabilistic image choice (PIC) task investigates the choice of viewing drug-related pictures as compared to other salient pictures (e.g., pleasant and unpleasant). This study aimed to develop and validate the PIC task for TUD and evaluate the associations between behavioral choice and tobacco craving, daily cigarette consumption, quit attempts and motivation to quit, and nicotine dependence (the Fagerstrom score). MethodsWe recruited 468 smokers and 121 nonsmokers using the Prolific online platform. Participants performed the PIC task twice (at a one-month interval) and completed other measures relevant to TUD. Resultscompared to nonsmokers, tobacco smokers selected to view significantly more tobacco images and less pleasant (non-drug reinforcer) images, a profile that remained stable at retest. Individual differences in choice of tobacco as compared to pleasant images on the PIC task were associated with craving but not with the other tobacco dependence measures, suggesting that the task may serve as a behavioral proxy measure of drug "wanting" rather than of cumulative nicotine exposure or physical dependence. Conclusionsthese results suggest that the PIC task can be a valuable tool for objectively assessing craving-associated tobacco seeking in TUD. Implications section, which should provide a brief description about what the study adds. Most of the current measures of tobacco use disorder (TUD) rely on self-reports of consumption, dependence and craving and do not take into consideration the role of drug-related cues in driving tobacco seeking. This study shows that the probabilistic image choice (PIC) task provides an objective, reliable proxy measure of tobacco image seeking behavior in cigarette smokers that is linked to craving (desire) for smoking but not to other measures of TUD. Therefore, the PIC task may be a useful complementary tool for the classification, diagnosis, and prognosis of TUD.

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↗

bioRxiv2022

Premorbid performances determine the deleterious effects of nigrostriatal degeneration and pramipexole on behavioural flexibility

Subtle cognitive impairment can occur early in the course of Parkinsons disease (PD) and may manifest under different forms of executive dysfunction such as impaired cognitive flexibility. The precise contribution of nigrostriatal dopaminergic neurodegeneration to these non-motor features of the disease is poorly known. Whether such cognitive impairment associated with the disease process may also predate and contribute to the development of neuropsychiatric side-effects following dopamine replacement therapy remains largely unknown. To address these issues, we investigated the respective contributions of nigrostriatal degeneration and chronic treatment with the dopamine D3-preferring agonist pramipexole on behavioural flexibility in a rat model of PD. Flexible, intermediate and inflexible rats were identified based on baseline assessment of behavioural flexibility using an operant set-shifting task. Nigrostriatal degeneration was induced by bilateral viral-mediated expression of A53T mutated human -synuclein in the substantia nigra pars compacta and behavioural flexibility was assessed after induction of nigrostriatal degeneration, and during chronic pramipexole treatment. Nigrostriatal degeneration impaired behavioural flexibility in flexible but not in inflexible rats. Pramipexole induced a decrease of behavioural flexibility that was exacerbated in lesioned rats and in the most flexible individuals. Furthermore, the deficits induced by pramipexole in lesioned rats affected different components of the task between flexible and inflexible individuals. This study demonstrates that nigrostriatal degeneration and pramipexole unequally impair behavioural flexibility, suggesting that the susceptibility to develop non-motor impairments upon treatment initiation could primarily depend on premorbid differences in behavioural flexibility.

neuroscience↗

bioRxiv2022

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↗

bioRxiv2019

Intercostal Space Prediction Using Deep Learning In Fully Endoscopic Mitral Valve Surgery

ObjectiveAbout 10 million people in Europe suffer from mitral valve incompetence. Majority of these entity is mitral valve prolapse in developed countries. Endoscopic mitral valve surgery is a relatively new procedure and preparation in the right intercostal space are crucial for success completion of the procedure. We aimed to explore clinical variables and chest X-rays in order to build most performant model that can predict the right intercostal space for thoracotomy.\n\nMethodsOverall 234 patients underwent fully endoscopic mitral valve surgery. All patients had preoperative two projection radiography. Intercostal space for right thoracotomy was decided by expert cardiac surgeons taking in consideration the height, weight, chest radiography, anatomical position of skin incision, nipple position and the sex. In order to predict the right intercostal space we have used clinical data and we have collected all radiographies and feed it to deep neural network algorithm. We have spitted the whole data-set into two subsets: training and testing data-sets. We have used clinical data and build an algorithm (Random Forest) in order to have reference model.\n\nResultsThe best-performing classifier was GoogLeNet neural network (now on we will reffera as Deep Learning) and had an AUC of 0.956. Algorithm based on clinical data (Random Forest) had AUC of 0.529 using only chest x-rays. The deep leaning algorithm predicted correctly in all cases the correct intercostal space on the training datasest except two ladies (96.08% ; with sensitivity of 97.06% and specificity 94.12 %, where the Random Forest was capable to predict right intercostal space in 60.78% cases with sensitivity of 93.33% and specificity 14.29 % (only clinical data).\n\nConclusionArtificial intelligence can be helpful to program the minimally invasive cardiac operation, for right intercostal space selection for thoracotomy, especially in non optimal thoraxes (example, obese short ladies). It learned from the standard imaging (thorax x-ray) which is easy, do routinely to every patient.

bioinformatics↗