RESUMO
AIM: Liver-expressed antimicrobial peptide 2 (LEAP2) dynamics in human plasma and its association with feeding behaviour remain poorly understood. Therefore, this study aims: (a) to investigate fasting LEAP2 in participants with normal weight or with overweight or mild obesity (OW/OB); (b) to study the association between fasting LEAP2 and anthropometric and metabolic traits, feeding behaviour, LEAP2 genetic variants and blood cell DNA methylation status; and (c) to ascertain postprandial changes in LEAP2 after high protein intake and the association with feeding behaviour and food intake. METHODS: Anthropometric and behavioural measures, genotyping, methylation profiling, plasma glucose and LEAP2 concentrations were assessed in 327 females and males. A subgroup of 123 participants received an ad libitum high-protein meal, and postprandial LEAP2 concentration and behavioural measures were assessed. RESULTS: LEAP2 concentration was higher in participants with OW/OB (p < 0.001) and in females (p < 0.001), and was associated with LEAP2 single nucleotide polymorphisms rs765760 (p = 0.012) and rs803223 (p = 0.019), but not with LEAP2 methylation status. LEAP2 concentration was directly related to glycaemia (p = 0.001) and fullness (p = 0.003) in participants with normal weight, whereas it was associated with body mass index (p = 0.018), waist circumference (p = 0.014) and motor impulsivity in participants with OW/OB (p = 0.005). A negative association with reward responsiveness was observed in participants with OW/OB (p = 0.023). LEAP2 concentration was inversely associated with food intake (p = 0.034) and decreased after a high-protein meal (p < 0.001), particularly in women (p = 0.002). CONCLUSION: Increased LEAP2 in participants with OW/OB is associated with behavioural characteristics of obesity. Our results show sexual dimorphism in LEAP2 concentration before and after food intake and highlight the role of LEAP2 in feeding regulation.
Assuntos
Proteínas Alimentares , Comportamento Alimentar , Comportamento Impulsivo , Estado Nutricional , Obesidade , Recompensa , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/metabolismo , Obesidade/psicologia , Obesidade/sangue , Proteínas Alimentares/administração & dosagem , Comportamento Alimentar/fisiologia , Período Pós-Prandial , Polimorfismo de Nucleotídeo Único , Sobrepeso/genética , Sobrepeso/metabolismo , Sobrepeso/sangue , Metilação de DNA , Jejum , Proteínas Sanguíneas , Peptídeos Catiônicos AntimicrobianosRESUMO
Previous studies from our laboratory have shown sex differences in the behavioral, molecular, and neurochemical manifestations of morphine withdrawal and they were related to an increased sensitivity to morphine effects in males. In addition, we observed an interaction between the GABAergic and opioid systems that could also be sex-dependent. Baclofen, a GABAB receptor agonist, prevented the somatic expression and the molecular and neurochemical changes induced by morphine withdrawal syndrome in mice. On the contrary, little is known about baclofen effects in the rewarding properties of morphine in male and female mice. The present study aimed to explore the effect of baclofen (1, 2 and 3 mg/kg, i.p.) pretreatment in the rewarding effects induced by morphine (7 mg/kg, s.c.) and its effect on c-Fos and brain-derived neurotrophic factor (BDNF) expression induced by the rewarding properties of morphine in prepubertal male and female mice. Baclofen (2 mg/kg) pretreatment prevented the rewarding effects of morphine only in male mice, while baclofen (3 mg/kg) reduced these effects in both sexes. Moreover, the rewarding effects of morphine were associated with a decrease of BDNF and c-Fos expression cingulate cortex, nucleus accumbens shell, cornu ammonis 1 (CA1), and cornu ammonis 3 (CA3) areas of the hippocampus only in male mice. In addition, baclofen pretreatment prevented these changes in BDNF, but not in c-Fos expression. In conclusion, our results show that GABAB receptors have a regulatory role in the rewarding effects of morphine that could be of interest for a potential future therapeutic application in opioid use disorders.
Assuntos
Baclofeno , Fator Neurotrófico Derivado do Encéfalo , Morfina , Proteínas Proto-Oncogênicas c-fos , Recompensa , Animais , Baclofeno/farmacologia , Masculino , Feminino , Morfina/farmacologia , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Agonistas dos Receptores de GABA-B/farmacologia , Caracteres Sexuais , Comportamento Animal/efeitos dos fármacos , Fatores SexuaisRESUMO
Olfaction is influenced by contextual factors, past experiences, and the animal's internal state. Whether this information is integrated at the initial stages of cortical odour processing is not known, nor how these signals may influence odour encoding. Here we revealed multiple and diverse non-olfactory responses in the primary olfactory (piriform) cortex (PCx), which dynamically enhance PCx odour discrimination according to behavioural demands. We performed recordings of PCx neurons from mice trained in a virtual reality task to associate odours with visual contexts to obtain a reward. We found that learning shifts PCx activity from encoding solely odours to a regime in which positional, contextual, and associative responses emerge on odour-responsive neurons that become mixed-selective. The modulation of PCx activity by these non-olfactory signals was dynamic, improving odour decoding during task engagement and in rewarded contexts. This improvement relied on the acquired mixed-selectivity, demonstrating how integrating extra-sensory inputs in sensory cortices can enhance sensory processing while encoding the behavioural relevance of stimuli.
Assuntos
Odorantes , Recompensa , Olfato , Animais , Camundongos , Olfato/fisiologia , Masculino , Córtex Olfatório/fisiologia , Córtex Piriforme/fisiologia , Camundongos Endogâmicos C57BL , Percepção Olfatória/fisiologia , Neurônios/fisiologia , Feminino , Discriminação Psicológica/fisiologiaRESUMO
Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300â¯s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600â¯s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300â¯s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.
Assuntos
Condicionamento Clássico , Condicionamento Operante , Extinção Psicológica , Animais , Extinção Psicológica/fisiologia , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Recompensa , Masculino , Reforço Psicológico , Feminino , Comportamento Animal/fisiologia , Bufonidae/fisiologia , Bufo arenarum/fisiologiaRESUMO
Most of the literature on the neural bases of human reward and punishment processing has used monetary gains and losses, but less is known about the neurophysiological mechanisms underlying the anticipation and consumption of other types of rewarding stimuli. In the present study, EEG was recorded from 19 participants who completed a modified version of the Monetary Incentive Delay (MID) task. During the task, cues providing information about potential future outcomes were presented to the participants. Then, they had to respond rapidly to a target stimulus to win money or listening to pleasant music, or to avoid losing money or listening to unpleasant music. Results revealed similar responses for monetary and music cues, with increased activity for cues indicating potential gains compared to losses. However, differences emerged in the outcome phase between money and music. Monetary outcomes showed an interaction between the type of the cue and the outcome in the Feedback Related Negativity and Fb-P3 ERPs and increased theta activity increased for negative feedbacks. In contrast, music outcomes showed significant interactions in the Fb-P3 and theta activities. These findings suggest similar neurophysiological mechanisms in processing cues for potential positive or negative outcomes in these two types of stimuli.
Assuntos
Antecipação Psicológica , Eletroencefalografia , Música , Recompensa , Humanos , Masculino , Feminino , Eletroencefalografia/métodos , Adulto Jovem , Antecipação Psicológica/fisiologia , Adulto , Sinais (Psicologia) , Potenciais Evocados/fisiologia , Encéfalo/fisiologia , Motivação/fisiologia , Estimulação Acústica/métodosRESUMO
It has been well established that a consolidated memory can be updated during the plastic state induced by reactivation. This updating process opens the possibility to modify maladaptive memory. In the present study, we evaluated whether fear memory could be updated to less-aversive level by incorporating hedonic information during reactivation. Thus, male rats were fear conditioned and, during retrieval, a female was presented as a social rewarding stimulus. We found that memory reactivation with a female (but not a male) reduces fear expression within-session and in the test, without presenting reinstatement or spontaneous recovery. Interestingly, this intervention impaired extinction. Finally, we demonstrated that this emotional remodeling to eliminate fear expression requires the activation of dopamine and oxytocin receptors during retrieval. Hence, these results shed new lights on the memory updating process and suggests that the exposure to natural rewarding information such as a female during retrieval reduces a previously consolidated fear memory.
Assuntos
Medo , Receptores de Ocitocina , Interação Social , Animais , Medo/fisiologia , Masculino , Ratos , Receptores de Ocitocina/metabolismo , Feminino , Memória/fisiologia , Extinção Psicológica/fisiologia , Receptores Dopaminérgicos/metabolismo , Condicionamento Clássico/fisiologia , Recompensa , Ratos Wistar , Consolidação da Memória/fisiologiaRESUMO
BACKGROUND: The impulsive choice is characterized by the preference for a small immediate reward over a bigger delayed one. The mechanisms underlying impulsive choices are linked to the activity in the Nucleus Accumbens (NAc), the orbitofrontal cortex (OFC), and the dorsolateral striatum (DLS). While the study of functional connectivity between brain areas has been key to understanding a variety of cognitive processes, it remains unclear whether functional connectivity differentiates impulsive-control decisions. METHODS: To study the functional connectivity both between and within NAc, OFC, and DLS during a delay discounting task, we concurrently recorded local field potential in NAc, OFC, and DLS in rats. We then quantified the degree of phase-amplitude coupling (PAC), coherence, and Granger Causality between oscillatory activities in animals exhibiting either a high (HI) or low (LI) tendency for impulsive choices. RESULTS: Our results showed a differential pattern of PAC during decision-making in OFC and NAc, but not in DLS. While theta-gamma PAC in OFC was associated with self-control decisions, a higher delta-gamma PAC in both OFC and NAc biased decisions toward impulsive choices in both HI and LI groups. Furthermore, during the reward event, Granger Causality analysis indicated a stronger NAcâOFC gamma contribution in the HI group, while the LI group showed a higher OFCâNAc gamma contribution. CONCLUSIONS: The overactivity in NAc during reward in the HI group suggests that exacerbated contribution of NAcCore can lead to an overvaluation of reward that biases the behavior toward the impulsive choice.
Assuntos
Tomada de Decisões , Desvalorização pelo Atraso , Comportamento Impulsivo , Núcleo Accumbens , Córtex Pré-Frontal , Recompensa , Animais , Núcleo Accumbens/fisiologia , Desvalorização pelo Atraso/fisiologia , Masculino , Tomada de Decisões/fisiologia , Ratos , Córtex Pré-Frontal/fisiologia , Comportamento Impulsivo/fisiologia , Comportamento de Escolha/fisiologiaRESUMO
This chapter (part one of a trilogy) summarizes the neurobiological foundations of endogenous opioids in the regulation of energy balance and eating behavior, dysregulation of which translates to maladaptive dietary responses in individuals with obesity and eating disorders, including anorexia, bulimia, and binge eating disorder. Knowledge of these neurobiological foundations is vital to researchers' and clinicians' understanding of pathophysiology as well as the science-based development of multidisciplinary diagnoses and treatments for obesity and eating disorders. We highlight mechanisms of endogenous opioids in both homeostatic and hedonic feeding behavior, review research on the dysregulation of food reward that plays a role in a wide array of obesity and disordered eating, and the clinical implications of neurobiological responses to food for current science-based treatments for obesity and eating disorders.
Assuntos
Comportamento Alimentar , Homeostase , Fome , Obesidade , Peptídeos Opioides , Humanos , Homeostase/fisiologia , Fome/fisiologia , Peptídeos Opioides/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Comportamento Alimentar/fisiologia , Transtornos da Alimentação e da Ingestão de Alimentos/metabolismo , Transtornos da Alimentação e da Ingestão de Alimentos/fisiopatologia , Saciação/fisiologia , Recompensa , Metabolismo Energético/fisiologia , Ingestão de Alimentos/fisiologia , AnimaisRESUMO
Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc). We evaluated behavior and neuronal firing after AIE (5 g/kg intragastric) or water (CON) in adult female rats. Both AIE and CON groups expressed a ST phenotype, and AIE marginally increased sign-tracking (ST) and decreased goal-tracking (GT) metrics. NAc neurons exhibited phasic firing patterns to the conditional stimulus (CS), with no differences between groups. In contrast, neuronal firing in the OFC of AIE animals was greater at CS onset and offset than in CON animals. During reward omission, OFC responses to CS offset normalized to CON levels, but enhanced OFC firing to CS onset persisted in AIE. We suggest that the enhanced OFC neural activity observed in AIE rats to the CS could contribute to behavioral inflexibility. Ultimately, AIE persistently impacts the neurocircuitry of reward-motivated behavior in female rats.
Assuntos
Etanol , Núcleo Accumbens , Córtex Pré-Frontal , Recompensa , Animais , Feminino , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Ratos , Etanol/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/fisiologia , Neurônios/fisiologia , Neurônios/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Sinais (Psicologia) , Ratos Sprague-DawleyRESUMO
Social insects live in communities where cooperative actions heavily rely on the individual cognitive abilities of their members. In the honey bee (Apis mellifera), the specialization in nectar or pollen collection is associated with variations in gustatory sensitivity, affecting both associative and non-associative learning. Gustatory sensitivity fluctuates as a function of changes in motivation for the specific floral resource throughout the foraging cycle, yet differences in learning between nectar and pollen foragers at the onset of food collection remain unexplored. Here, we examined nectar and pollen foragers captured upon arrival at food sources. We subjected them to an olfactory proboscis extension reflex (PER) conditioning using a 10% sucrose solution paired (S10%+P) or unpaired (S10%) with pollen as a co-reinforcement. For non-associative learning, we habituated foragers with S10%+P or S10%, followed by dishabituation tests with either a 50% sucrose solution paired (S50%+P) or unpaired (S50%) with pollen. Our results indicate that pollen foragers show lower performance than nectar foragers when conditioned with S10%. Interestingly, performance improves to levels similar to those of nectar foragers when pollen is included as a rewarding stimulus (S10%+P). In non-associative learning, pollen foragers tested with S10%+P displayed a lower degree of habituation than nectar foragers and a higher degree of dishabituation when pollen was used as the dishabituating stimulus (S10%+P). Altogether, our results support the idea that pollen and nectar honey bee foragers differ in their responsiveness to rewards, leading to inter-individual differences in learning that contribute to foraging specialization.