Current Pharmaceutical Design - Volume 26, Issue 20, 2020

A complex interplay of peripheral and central signaling mechanisms within the body of an organism maintains energy homeostasis. In addition, energy/food intake is modified by various external factors (e.g., palatability, food availability, social and environmental triggers). Highly palatable foods can provoke maladaptive feeding behavior, which in turn disrupts normal homeostatic regulation resulting in numerous health consequences. Furthermore, neuroendocrine peptides, traditionally considered to regulate appetite and energy homeostasis, also control the intake and reinforcing properties of alcohol and drugs of abuse. Therefore, dysregulated eating as a result of a hedonic/binge-like intake of hyper-palatable food may impact alcohol drinking behavior. Relevant in this case is the fact that eating disorders are highly comorbid with several neuropsychiatric conditions, including alcohol use disorder. The present review is intended to summarize the neurobiological and functional consequences of hedonic feeding on alcohol intake.

How people become addicted to cigarette smoking and remain addicted despite repeated attempts to quit requires piecing together a rather complex puzzle. The present review contextualizes the role of nicotine and smoking sensory stimulation on maintaining smoking, describes nicotine’s effects on feeding behavior and body weight, and explores the impact of smoking outcome expectancies, including the belief that nicotine suppresses appetite and body weight, on the decision to smoke or vape (use of e-cigarettes). The analysis concludes with a review of rat models of human nicotine intake that attempt to isolate the effects of nicotine on appetite and weight gain. Animal research replicates with relative closeness phenomena observed in smokers, but the rat model falls short of replicating the long-term weight gain observed post-smoking cessation.

People with Binge Eating Disorder (BED) exhibit heightened sensitivity to rewarding stimuli and elevated activity in reward-related brain regions, including the orbitofrontal cortex (OFC), ventral striatum (VS) and insula, during food-cue exposure. BED has also been associated with altered patterns of functional connectivity during resting-state. Investigating neural connectivity in the absence of task stimuli provides knowledge about baseline communication patterns that may influence the behavioural and cognitive manifestation of BED. Elevated resting-state functional connectivity (rsFC) between reward-related brain regions may contribute to uncontrolled eating bouts observed in BED, through heightened food-cue sensitivity and food-craving. The impact of homeostatic state on rsFC of the reward system has not yet been investigated in people with BED. Homeostatic dysfunction is a key driver of excessive food consumption in obesity, whereby rsFC between rewardrelated brain regions does not attenuate during satiety. Future studies should investigate BED related differences in rsFC within the reward system during hunger and satiety, in order to determine whether individuals with BED display an abnormal neural response to changes in homeostatic state. This knowledge would further enhance current understandings of the mechanisms contributing to BED, potentially implicating both reward and homeostatic dysfunctions as drivers of BED.

As manifestations of excessive and uncontrolled intake, obesity and drug addiction have generated much research aimed at identifying common neuroadaptations that could underlie both disorders. Much work has focused on changes in brain reward and motivational circuitry that can overexcite eating and drug-taking behaviors. We suggest that the regulation of both behaviors depends on balancing excitation produced by stimuli associated with food and drug rewards with the behavioral inhibition produced by physiological “satiety” and other stimuli that signal when those rewards are unavailable. Our main hypothesis is that dysregulated eating and drug use are consequences of diet- and drug-induced degradations in this inhibitory power. We first outline a learning and memory mechanism that could underlie the inhibition of both food and drug-intake, and we describe data that identifies the hippocampus as a brain substrate for this mechanism. We then present evidence that obesitypromoting western diets (WD) impair the operation of this process and generate pathophysiologies that disrupt hippocampal functioning. Next, we present parallel evidence that drugs of abuse also impair this same learning and memory process and generate similar hippocampal pathophysiologies. We also describe recent findings that prior WD intake elevates drug self-administration, and the implications of using drugs (i.e., glucagon-like peptide- 1 agonists) that enhance hippocampal functioning to treat both obesity and addiction are also considered. We conclude with a description of how both WD and drugs of abuse could initiate a “vicious-cycle” of hippocampal pathophysiology and impaired hippocampal-dependent behavioral inhibition.

Bipolar disorder and major depression are associated with significant disability, morbidity, and reduced life expectancy. People with mood disorders have shown higher ratios of unhealthy lifestyle choices, including poor diet quality and suboptimal nutrition. Diet and nutrition impact on brain /mental health, but cognitive outcomes have been less researched in psychiatric disorders. Neurocognitive dysfunction is a major driver of social dysfunction and a therapeutic target in mood disorders, although effective cognitive-enhancers are currently lacking. This narrative review aimed to assess the potential cognitive benefits of dietary and nutritional interventions in subjects diagnosed with mood disorders. Eight clinical trials with nutrients were identified, whereas none involved dietary interventions. Efficacy to improve select cognitive deficits has been reported, but results are either preliminary or inconsistent. Methodological recommendations for future cognition trials in the field are advanced. Current evidence and future views are discussed from the perspectives of precision medicine, clinical staging, nutritional psychiatry, and the brain-gut-microbiota axis.

Energy homeostasis is achieved, in part, by metabolic signals that regulate the incentive motivating effects of food and its cues, thereby driving or curtailing procurement and consumption. The neural underpinnings of these regulated incentive effects have been identified as elements within the mesolimbic dopamine pathway. A separate line of research has shown that most drugs with abuse liability increase dopamine transmission in this same pathway and thereby reinforce self-administration. Consequently, one might expect shifts in energy balance and metabolic signaling to impact drug abuse risk. Basic science studies have yielded numerous examples of drug responses altered by diet manipulation. Considering the prevalence of weight loss dieting in Western societies, and the anorexigenic effects of many abused drugs themselves, we have focused on the CNS and behavioral effects of food restriction in rats. Food restriction has been shown to increase the reward magnitude of diverse drugs of abuse, and these effects have been attributed to neuroadaptations in the dopamine-innervated nucleus accumbens. The changes induced by food restriction include synaptic incorporation of calcium-permeable AMPA receptors and increased signaling downstream of D1 dopamine receptor stimulation. Recent studies suggest a mechanistic model in which concurrent stimulation of D1 and GluA2-lacking AMPA receptors enables increased stimulus-induced trafficking of GluA1/GluA2 AMPARs into the postsynaptic density, thereby increasing the incentive effects of food, drugs, and associated cues. In addition, the established role of AMPA receptor trafficking in enduring synaptic plasticity prompts speculation that drug use during food restriction may more strongly ingrain behavior relative to similar use under free-feeding conditions.

Eating is necessary for survival, but it is also one of the great pleasures enjoyed by human beings. Research to date shows that palatable food can be rewarding in a similar way to drugs of abuse, indicating considerable comorbidity between eating disorders and substance-use disorders. Analysis of the common characteristics of both types of disorder has led to a new wave of studies proposing a Gateway Theory of food as a vulnerability factor that modulates the development of drug addiction. The homeostatic and hedonic mechanisms of feeding overlap with some of the mechanisms implicated in drug abuse and their interaction plays a crucial role in the development of drug addiction. Studies in animal models have shown how palatable food sensitizes the reward circuit and makes individuals more sensitive to other substances of abuse, such as cocaine or alcohol. However, when palatable food is administered continuously as a model of obesity, the consequences are different, and studies provide controversial data. In the present review, we will cover the main homeostatic and hedonic mechanisms that regulate palatable food intake behavior and will explain, using animal models, how different types of diet and their intake patterns have direct consequences on the rewarding effects of psychostimulants and ethanol.

Omega-3 (N3) fatty acids are dietary nutrients that are essential for human health. Arguably, one of their most critical contributions to health is their involvement in the structure and function of the nervous system. N3 fatty acids accumulate in neuronal membranes through young adulthood, becoming particularly enriched in a brain region known to be the locus of cognitive control of behavior-the prefrontal cortex (PFC). The PFC undergoes a surge in development during adolescence, coinciding with a life stage when dietary quality and intake of N3 fatty acids tend to be suboptimal. Such low intake may impact neurodevelopment and normative development of cognitive functions suggested to be protective for the risk of subsequent substance and alcohol use disorders (UD). While multiple genetic and environmental factors contribute to risk for and resilience to substance and alcohol use disorders, mounting evidence suggests that dietary patterns early in life may also modulate cognitive and behavioral factors thought to elevate UD risk (e.g., impulsivity and reward sensitivity). This review aims to summarize the literature on dietary N3 fatty acids during childhood and adolescence and risk of executive/ cognitive or behavioral dysfunction, which may contribute to the risk of subsequent UD. We begin with a review of the effects of N3 fatty acids in the brain at the molecular to cellular levels–providing the biochemical mechanisms ostensibly supporting observed beneficial effects. We continue with a review of cognitive, behavioral and neurodevelopmental features thought to predict early substance and alcohol use in humans. This is followed by a review of the preclinical literature, largely demonstrating that dietary manipulation of N3 fatty acids contributes to behavioral changes that impact drug sensitivity. Finally, a review of the available evidence in human literature, suggesting an association between dietary N3 fatty and neurodevelopmental profiles associated with risk of adverse outcomes including UD. We conclude with a brief summary and call to action for additional research to extend the current understanding of the impact of dietary N3 fatty acids and the risk of drug and alcohol UD.

Unhealthy diet and alcohol are serious health problems, especially in adolescents and young adults. “Binge” is defined as the excessive and uncontrolled consumption of food (binge eating) and alcohol (binge drinking). Both behaviors are frequent among young people and have a highly negative impact on health and quality of life. Several studies have explored the causes and risk factors of both behaviors, and the evidence concludes that there is a relationship between the two behaviors. In addition, some research postulates that binge eating is a precipitating factor in the onset and escalation of excessive alcohol consumption, while other studies suggest that alcohol consumption leads to excessive and uncontrollable food consumption. Given that no review has yet been published regarding the directionality between the two behaviors, we have set out to provide an upto- date overview of binge eating and binge drinking problems, analyzing their commonalities and differences, and their uni- and bidirectional associations. In addition, we explore the reasons why young people tend to engage in both behaviors and consider directions for future research and clinical implications.

The interaction between meal timing and light regulates circadian rhythms in mammals and not only determines the sleep-wake pattern but also the activity of the endocrine system. Related with that, the necessity to fulfill energy needs is a driving force that requires the participation of cognitive skills whose performance has been shown to undergo circadian variations. These facts have led to the concept that cognition and feeding behaviour can be analysed from a chronobiological perspective. In this context, research carried out during the last two decades has evidenced the link between feeding behaviour/nutritional habits and cognitive processes, and has highlighted the impact of circadian disorders on cognitive decline. All that has allowed hypothesizing a tight relationship between nutritional factors, chronobiology, and cognition. In this connection, experimental diets containing elevated amounts of fat and sugar (high-fat diets; HFDs) have been shown to alter in rodents the circadian distribution of meals, and to have a negative impact on cognition and motivational aspects of behaviour that disappear when animals are forced to adhere to a standard temporal eating pattern. In this review, we will present relevant studies focussing on the effect of HFDs on cognitive aspects of behaviour, paying particular attention to the influence that chronobiological alterations caused by these diets may have on hippocampaldependent cognition.

In recent years, there has been an exciting focus of research attempting to understand neuropsychiatric disorders from a holistic perspective in order to determine the role of gut microbiota in the aetiology and pathogenesis of such disorders. Thus, the possible therapeutic benefits of targeting gut microbiota are being explored for conditions such as stress, depression or schizophrenia. Growing evidence indicates that there is bidirectional communication between gut microbiota and the brain that has an effect on normal CNS functioning and behavioural responses. Alcohol abuse damages the gastrointestinal tract, alters gut microbiota and induces neuroinflammation and cognitive decline. The relationship between alcohol abuse and hypothalamic-pituitary-adrenal axis activation, inflammation and immune regulation has been well documented. In this review, we explore the connection between microbiota, brain function and behaviour, as well as the mechanisms through which alcohol induces microbiota dysbiosis and intestinal barrier dysfunction. Finally, we propose the study of psychobiotics as a novel pharmaceutical strategy to treat alcohol use disorders.