Ghrelin and Glucagon-Like Peptide-1: A Gut-Brain Axis Battle for Food Reward

Eating behaviors are influenced by the reinforcing properties of foods that can favor decisions driven by reward incentives over metabolic needs. These food reward-motivated behaviors are modulated by gut-derived peptides such as ghrelin and glucagon-like peptide-1 (GLP-1) that are well-established to promote or reduce energy intake, respectively. In this review we highlight the antagonizing actions of ghrelin and GLP-1 on various behavioral constructs related to food reward/reinforcement, including reactivity to food cues, conditioned meal anticipation, effort-based food-motivated behaviors, and flavor-nutrient preference and aversion learning. We integrate physiological and behavioral neuroscience studies conducted in both rodents and human to illustrate translational findings of interest for the treatment of obesity or metabolic impairments. Collectively, the literature discussed herein highlights a model where ghrelin and GLP-1 regulate food reward-motivated behaviors via both competing and independent neurobiological and behavioral mechanisms.     

Loss of tolerance to morphine after a change in route of administration: control of within-session tolerance by interoceptive conditioned stimuli

Tolerance to morphine analgesia (tail-immersion test) was examined after manipulation of two aspects of a tolerance test: 1) the route of drug administration and 2) the time interval between the test dosing and the tolerance test. The intravenous (IV) and intraperitoneal (IP) routes were used, together with a novel test for tolerance in which the test morphine was infused IV just 2 min before measuring the opiate effect. The first experiment validated this test as an assay for tolerance by examining the log dose-response (LDR) curve changes produced by daily IP injection with 0, 20 or 200 mg/kg morphine; the IV test confirmed the expected parallel shift to the right and flattening of the LDR curve. In the second experiment, all rats of two groups were injected once daily for 3 weeks with 20 mg/kg morphine and with saline except that one group received the morphine IV (and saline IP), the other morphine IP (saline IV). The results indicated route-specific tolerance. On a test using 20 mg/kg given IV morphine, tolerance was significantly greater in rats treated with IV morphine than in those treated IP. However, a larger effect on tolerance was produced by a pretest application of 5 mg/kg morphine 30 min before the actual tolerance test. This manipulation was designed to prime short-term, adaptive processes hypothesized to occur within a normal tolerance test session as morphine is taking effect. The tolerance on the test increased (equivalent to 2 to 3 fold shift in the LDR curve) when the pretest morphine was given with the same route as the chronic morphine, regardless of treatment group. It was concluded that opiate tolerance may be modulated by conditioned stimuli produced by morphine acting through different routes. These interoceptive cues appear to modulate rapidly acquired and short-lived adaptive processes taking place within a given test session.     

Effects of handwriting exercise on functional outcome in Parkinson disease: A randomized controlled trial

Parkinson disease (PD) patients frequently experience micrographia and difficulty writing, which could potentially impact their quality of life. This study aimed to determine whether handwriting exercise could improve fine manual motor function in PD. The study was a randomized controlled trial assessing the efficacy of a 4-week handwriting exercise using a newly developed handwriting practice book. The primary endpoint was an improvement in the time used to complete the handwriting test. Secondary endpoints were accuracy of the writing performance, patient’s subjective rating scale of their handwriting and a UPDRS part III motor examination. Of a total of 46 subjects, 23 were randomly assigned to the handwriting exercise group. After 4 weeks, the mean time used to complete the test was significantly lower in the exercise group, compared to the control group (143.43 ± 34.02 vs. 175 ± 48.88 s, p = 0.015). Mean time used to complete the handwriting test decreased from the baseline by 16.16% in the exercise group, but increased by 3.63% in the control group (p < 0.001). Significant improvements were also observed by assessing the subjective rating scale and the UPDRS part III scores. The 4-week handwriting exercise using the studied handwriting practice book appears to promote an improvement in writing speed and motor function of hands. The optimal duration and frequency of the exercise, the quantity and characteristic of the letters in the handwriting practice book, and the benefits of the exercise in other languages merit further studies.     

Dynamic integration of information about salience and value for saccadic eye movements

Humans shift their gaze to a new location several times per second. It is still unclear what determines where they look next. Fixation behavior is influenced by the low-level salience of the visual stimulus, such as luminance, contrast, and color, but also by high-level task demands and prior knowledge. Under natural conditions, different sources of information might conflict with each other and have to be combined. In our paradigm, we trade off visual salience against expected value. We show that both salience and value information influence the saccadic end point within an object, but with different time courses. The relative weights of salience and value are not constant but vary from eye movement to eye movement, depending critically on the availability of the value information at the time when the saccade is programmed. Short-latency saccades are determined mainly by salience, but value information is taken into account for long-latency saccades. We present a model that describes these data by dynamically weighting and integrating detailed topographic maps of visual salience and value. These results support the notion of independent neural pathways for the processing of visual information and value.     

Reduced sense of agency in chronic schizophrenia with predominant negative symptoms

Self-disturbances in schizophrenia have been regarded as a fundamental vulnerability marker for this disease, and have begun to be studied from the standpoint of an abnormal “sense of agency (SoA)” in cognitive neuroscience. To clarify the nature of aberrant SoA in schizophrenia, it needs to be investigated in various clinical subtypes and stages. The residual type of chronic schizophrenia with predominant negative symptoms (NS) has never been investigated for SoA. Accordingly, we investigated SoA by an original agency attribution task in NS-predominant schizophrenia, and evaluated the dynamic interplay between the predictive and postdictive components of SoA in the optimal cue integration framework. We studied 20 patients with NS-predominant schizophrenia, and compared with 30 patients with paranoid-type schizophrenia and 35 normal volunteers. NS-predominant schizophrenia showed markedly diminished SoA compared to normal controls and paranoid-type schizophrenia, indicating a completely opposite direction in agency attribution compared with excessive SoA demonstrated in paranoid-type schizophrenia. Reduced SoA was detected in experimental studies of schizophrenia for the first time. According to the optimal cue integration framework, these results indicate that there was no increase in compensatory contributions of the postdictive processes despite the existence of inadequate predictions, contrary to the exaggerated postdictive component in paranoid-type schizophrenia.     

Communicating hunger and satiation in the first 2 years of life: a systematic review

Responsive feeding has been identified as important in preventing overconsumption by infants. However, this is predicated on an assumption that parents recognise and respond to infant feeding cues. Despite this, relatively little is understood about how infants engage parental feeding responses. Therefore, the aim of this systematic review was to identify what is known about infant communication of hunger and satiation and what issues impact on the expression and perception of these states. A search of Medline, CINAHL, Web of Science, PsycINFO, Science Direct and Maternal and Infant care produced 27 papers. Eligibility criteria included peer reviewed qualitative and/or quantitative publications on feeding behaviours, hunger, and satiation/satiety cues of typically developing children in the first 2 years of life. Papers published between 1966 and 2013 were included in the review. The review revealed that feeding cues and behaviours are shaped by numerous issues, such as infants' physical attributes, individual psychological factors and environmental factors. Meanwhile, infant characteristics, external cues and mothers' own characteristics affect how feeding cues are perceived. The existing literature provides insights into many aspects of hunger and satiation in infancy; however, there are significant gaps in our knowledge. There is a lack of validated tools for measuring hunger and satiation, a need to understand how different infant characteristics impact on feeding behaviour and a need to extricate the respective contributions of infant and maternal characteristics to perceptions of hunger and satiation. Further research is also recommended to differentiate between feeding driven by liking and that driven by hunger.     

某地区部队官兵皮肤病的调查分析及防治对策

目的调查长白地区部队皮肤病发生情况,分析其发病原因,为防止提供科学依据。方法采用普查法,对986例长白部队官兵进行皮肤病流行病学调查。结果检测出皮肤病190例,发病率为19%。感染性皮肤病、皮肤附属器疾病及真菌性皮肤病发病率最高。结论部队官兵常见皮肤病为感染性皮肤病、皮肤附属器疾病及真菌性皮肤病;驻地环境、高强度训练及皮肤病防治知识缺乏时长白地区部队皮肤病发生的主要原因;应加强皮肤病的防治宣传,采取有效科学方法进行防治,提高部队军医的皮肤诊治水平是主要的防治措施。     

Variation within the serotonin (5-HT) 5-HT2C receptor system aligns with vulnerability to cocaine cue reactivity

Cocaine dependence remains a challenging public health problem with relapse cited as a major determinant in its chronicity and severity. Environmental contexts and stimuli become reliably associated with its use leading to durable conditioned responses (‘cue reactivity'') that can predict relapse as well as treatment success. Individual variation in the magnitude and influence of cue reactivity over behavior in humans and animals suggest that cue-reactive individuals may be at greater risk for the progression to addiction and/or relapse. In the present translational study, we investigated the contribution of variation in the serotonin (5-HT) 5-HT_2C receptor (5-HT_2CR) system in individual differences in cocaine cue reactivity in humans and rodents. We found that cocaine-dependent subjects carrying a single nucleotide polymorphism (SNP) in the HTR2C gene that encodes for the conversion of cysteine to serine at codon 23 (Ser23 variant) exhibited significantly higher attentional bias to cocaine cues in the cocaine-word Stroop task than those carrying the Cys23 variant. In a model of individual differences in cocaine cue reactivity in rats, we identified that high cocaine cue reactivity measured as appetitive approach behavior (lever presses reinforced by the discrete cue complex) correlated with lower 5-HT_2CR protein expression in the medial prefrontal cortex and blunted sensitivity to the suppressive effects of the selective 5-HT_2CR agonist WAY163909. Our translational findings suggest that the functional status of the 5-HT_2CR system is a mechanistic factor in the generation of vulnerability to cocaine-associated cues, an observation that opens new avenues for future development of biomarker and therapeutic approaches to suppress relapse in cocaine dependence.     

Classical conditioning in humans: nicotine as CS and alcohol as US

Animal studies suggest that drug effects can act as conditioned stimuli for various unconditioned stimuli including the effects of other drugs. The current study investigated drug-drug conditioning in human subjects. Sixteen subjects were given subcutaneous injections of either nicotine or saline before consumption of an alcoholic or soft drink in each of eight sessions. Across sessions the content of the injections was established as a reliable predictor of the alcoholic content of the drink. Physiological, subjective, and behavioural responses to the injections were used as indices of conditioning. Skin conductance measures obtained following the injections changed across trials in a way consistent with a conditioned response though patterns of change on cardiac inter-beat interval were less clear. However, neither behavioural nor subjective measures showed conditioning effects. In view of the number of variables studied the evidence for the development of conditioned responding on physiological measures must be suspected of being a type I error and is in need of replication. Subjects' reports revealed that nicotine and saline injections were difficult to discriminate. This would have weakened conditioning effects. Suggestions are made for improvements in the design of future studies of drug-drug conditioning in human subjects.