Food scarcity, neuroadaptations, and the pathogenic potential of dieting in an unnatural ecology: Binge eating and drug abuse

Abstract

In the laboratory, food restriction has been shown to induce neuroadaptations in brain reward circuitry which are likely to be among those that facilitate survival during periods of food scarcity in the wild. However, the upregulation of mechanisms that promote foraging and reward-related learning may pose a hazard when food restriction is self-imposed in an ecology of abundant appetitive rewards. For example, episodes of loss of control during weight-loss dieting, use of drugs with addictive potential as diet aids, and alternating fasting with alcohol consumption in order to avoid weight gain, may induce synaptic plasticity that increases the risk of enduring maladaptive reward-directed behavior. In the present mini-review, representative basic research findings are outlined which indicate that food restriction alters the function of mesoaccumbens dopamine neurons, potentiates cellular and behavioral responses to D-1 and D-2 dopamine receptor stimulation, and increases stimulus-induced synaptic insertion of AMPA receptors in nucleus accumbens. Possible mechanistic underpinnings of increased drug reward magnitude, drug-seeking, and binge intake of sucrose in food-restricted animal subjects are discussed and possible implications for human weight-loss dieting are considered.

Introduction

In recent years there has been interest in the possible therapeutic use of controlled caloric restriction to induce the physiological and behavioral adaptations which accompany food scarcity in the wild. These adaptive responses are diverse and are generally aimed at conserving energy, prolonging survival, and promoting foraging and procurement of food. Consequently, caloric restriction has been reported to reduce oxidative stress, lower the risk of cardiovascular disease, increase resistance to neurotoxins, slow cognitive decline with age, and increase lifespan in many species (e.g., [1], [2], [3]). In addition, restricted feeding has been reported to exert mood-elevating and analgesic effects in humans [4], antidepressant and anxiolytic effects in animal models [5], [6], [7], [8], and increase incentive motivational responses in humans and rodents [9], [10], [11], [12], [13]. Neurophysiological correlates of the robust behavioral phenotype of the food-restricted subject were recently investigated using c-fos immunohistochemistry. Chronically food-restricted rats exposed to a nonthreatening novel environment displayed increased activation throughout a network of structures involved in antidepressant efficacy and incentive motivation, including ventral tegmental area, nucleus accumbens, and the piriform, anterior cingulate, and secondary motor cortices (Antoine, Austin, Stone and Carr, in preparation).

While controlled caloric restriction may be sustainable and beneficial when embedded within a supportive cognitive or social framework, weight-loss dieting in an ecology of abundant appetitive rewards has the potential to engender maladaptive compulsive behavior. Restrained eating often leads to loss of control, binging, and counterproductive weight gain [14], [15], [16], [17], and severe dieting is a risk factor for binge pathology [18]. Moreover, associations between food restriction, binge pathology, and substance abuse have been observed in clinical populations [19], [20], college students [21] and, most recently, high school students [22], [23]. The deliberate pairing of food restriction and drugs of abuse is not an uncommon practice, as in the use of tobacco and psychostimulants for appetite suppression [24], [25] or the increasingly popular “drunkorexia” among college-age women (i.e., fasting during the day in order to binge drink at night without weight gain) [26]. In light of the shared neural substrates of ingestive behavior and drug abuse [27], [28], [29], [30], and the neuroadaptations induced by food restriction to be described below, the neuroplastic changes which underlie drug addiction [31] may develop in response to supranormally rewarding foods, and occur more readily in response to drugs, if subjects are repeatedly exposed during food restriction.