Examining the addictive-like properties of binge eating using an animal model of sugar dependence.

The increase in the incidence of obesity and eating disorders has encouraged research efforts aimed at understanding the etiology of abnormal eating behaviors. Clinical reports have led to the suggestion that some individuals may develop addictive-like behaviors when consuming palatable foods. Binge eating is a behavioral component of bulimia and obesity and has also become increasingly common in nonclinical populations in our society. This review summarizes the behavioral and neurochemical similarities between binge eating of palatable foods and the administration of drugs of abuse. An animal model of bingeing on sugar is used to illustrate behaviors found with some drugs of abuse, such as opiate-like withdrawal signs, enhanced intake following abstinence, and cross-sensitization. Related neurochemical changes commonly observed with drugs of abuse, including changes in dopamine and acetylcholine release in the nucleus accumbens, can also be found with bingeing on sugar. These neurochemical alterations are exacerbated when animals binge on sugar while at a low body weight or when the food they ingest is purged. Drawing on other animal models and the clinical literature, parallels between drug abuse and binge-eating behavior are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Prefrontal and striatal dopamine metabolism during enhanced rebound hyperphagia induced by space restriction--a rat model of binge eating

BACKGROUND: Several lines of evidence indicate that abnormalities in brain dopamine and serotonin metabolism may play an important role in bulimia nervosa. However, the regional neurochemical mechanism of the binge eating is poorly understood. Our purpose was to elucidate brain neurochemical mechanisms of binge eating using a rat model. METHODS: The dopamine release and metabolism in the prefrontal cortex (PFC) and in the ventrolateral striatum (VLS) of rats were studied using microdialysis during enhanced rebound hyperphagia induced by space restriction (an animal model of binge eating). RESULTS: The rats showed rebound hyperphagic state when they were released from scheduled feeding (2 hours/day feeding for 7 days). The hyperphagia was further enhanced when they were put in a space-restricted cage where their mobility was restricted. Dopamine release and metabolism were increased both in the PFC and in the VLS during the enhanced rebound hyperphagia. CONCLUSIONS: These results tentatively suggest that increased dopamine release and metabolism in the PFC and in the VLS may be related to space restriction and to activation of motor function involved in feeding behavior, respectively. The enhanced rebound hyperphagia induced by space restriction may be useful as an animal model of binge eating.     

Role of unconditioned and conditioned drug effects in the self-administration of opiates and stimulants.

Reviews recent behavioral and neuropharmacological findings, which suggest that opiate and stimulant drugs act on common neurochemical systems of the brain to generate positive appetitive states that maintain drug-taking behavior. CSs associated with these drugs arouse neural states that mimic features of those produced by the drugs themselves and thereby serve to increase the effectiveness of drug-related stimuli and to increase the probability of drug-related thoughts and actions. This positive incentive account of compulsive drug use contrasts with the drive-reduction view that continued drug use depends primarily on efforts to reduce or to avoid symptoms of withdrawal, and that conditioned stimuli initiate and maintain drug-taking behavior through the elicitation of withdrawal-like, drug-opposing CRs. (4 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Daily occupational stressors and marital behavior.

This study examined daily fluctuations in marital behavior (anger and withdrawal) as a function of same-day job stressors, using hierarchical linear modeling (HLM). Forty-three couples provided daily diary reports of their workload and negative social interactions at work on 5 consecutive days. Within-subject analyses demonstrate that husbands and wives reported greater marital anger and withdrawal following negative social interactions at work, and wives reported greater marital anger and withdrawal following days of heavy workload. Mediation analyses provide support for the negative mood spillover hypothesis (e.g., workload no longer predicted wives' marital anger when controlling for negative mood). Between-subjects analyses suggest that spouses in high-conflict families may be especially vulnerable to the effects of job stressors on marital interaction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alpha-linolenic acid deficiency modifies distractibility but not anxiety and locomotion in rats during aging

In rodents, chronic dietary alpha-linolenic acid deficiency decreases learning and memory and alters dopaminergic and serotoninergic neurotransmission. However, these two neurotransmitter systems are related mainly to attention, emotion and locomotion. Therefore, we decided to investigate the effects of dietary alpha-linolenic acid deficiency in rats tested with animal models of distractibility (the distractometer procedure), anxiety (the elevated plus maze) and ambulatory activity (a circular corridor). Moreover, because these neurochemical modifications persist during aging, we decided to study the effects of aging on these behaviors by using rats aged 2, 6, 12 and 24 mo. An age-related decline in distractibility was observed that was accelerated by linolenic acid deficiency. Indeed, an age-related reduction in distractibility was found in so far as distraction time was reduced at the age of 12 mo in controls and at the age of 24 mo in deficient groups compared with 2-mo-old rats. Moreover, distraction time was significantly lower in 6- and 24-mo-old rats fed a deficient diet compared with age-matched controls. Anxiety was not modified by diet or age. Finally, a parallel decrease in locomotion was exhibited by rats fed both diets between 6 and 12 mo of age. Locomotion was not modified by diet. These results show that dietary alpha-linolenic deficiency alters behavior in a very specific way; distractibility is modified by diet, whereas anxiety and locomotion are not, suggesting that particular brain areas may be altered.     

Preliminary results of a nutritional survey in a sample of 35,000 Italian schoolchildren

An investigation of the nutrient intake of a large-scale sample (n = 35,072), drawn from the Italian school-age population (7-10 years) was carried out in a nationwide survey of nutritional patterns. Friuli, the Piedmont, Latium and Sicily regions were selected as representative of the nation's north-south and east-west socio-economic divisions. A food frequency questionnaire was used to assess nutritional intake. Traditional methods of 24-h dietary recall and a weighted food diary were used in subsamples to assess the validity of the food frequency questionnaire. Our data suggest that the average diet of Italian schoolchildren is rich in protein (especially animal proteins) and lipids (prevalently saturated fatty acids), but that carbohydrate and fibre intakes remain generally low. The relatively low calcium intake among girls and a widespread, more than adequate iron intake are also noteworthy. The food and nutrient intakes assessed suggest a dietary pattern with several positive points, but also reveal potential hazards for a wider population spectrum. The type of large-scale nutritional monitoring with a multi-method approach can be used in Italy and elsewhere to describe the dietary trends of a school-age population.     

Neurobiology

The role of neuropeptide Y (NPY), leptin and 5-HT and other neurotransmitters implicated in the regulation of energy balance are only now being fully investigated. Little is known about how they may interact with each other in this complex process. In evolutionary terms, the availability of excess food, and the risk of obesity, is only a recent occurrence in humans. Man, and perhaps other species, may not have developed a specialised neurochemical system for adjusting food intake during obesity. Hence perturbation of a single system, such as hypothalamic NPY or leptin, is unlikely to be directly responsible for the development of most obesity. In contrast, periods of food deprivation and partial starvation have been common in the animal kingdom and the multitude of neurotransmitters implicated in energy balance are more likely to be directed towards increasing food consumption and conserving energy than reducing appetite and increasing thermogenesis in the presence of excess. The last few years have witnessed rapid advances in the understanding of the fundamental mechanisms that regulate body weight and fat content. This progress will undoubtedly continue in the future, and it is hoped that this will be rewarded with the development of new drugs to treat obesity. At present, however, it is unclear whether NPY, leptin, or other apparently strong candidates will be the winner in the lucrative race for the ideal anti-obesity drug.     

Effect of yohimbine on the development of morphine dependence in the rat: lack of involvement of cortical beta-adrenoceptor modifications

The alpha-2 receptor antagonist yohimbine has been previously shown to prevent the development of morphine dependence in a rat behavioral model. This study was directed to clarify the mechanism of this interaction, which is presently unknown. Since upregulation of cortical beta-adrenoceptors has been suggested to be involved in morphine withdrawal, we have tested the possible correlation between receptor density and withdrawal behaviors in the presence of yohimbine. Sprague-Dawley male rats received a s.c. suspension of morphine (300 mg/kg) or the vehicle. Animals received saline or yohimbine (4 mg/kg, IP) 24, 28, 48 and 52 h after morphine and finally naloxone (1 mg/kg i.p) at 72 h; the subsequent signs of withdrawal (mainly wet-dog shakes and escape attempts) were recorded and the cerebral cortex dissected to study [3H]-CGP 12177 binding. Morphine-treated animals displayed a marked withdrawal behavior together with beta-adrenoceptor upregulation; nevertheless, these effects were not correlated. As expected, yohimbine prevented morphine withdrawal behavior but did not reverse the beta-adrenoceptor upregulation induced by the opiate. These results confirm previous evidence against the involvement of beta-adrenoceptor upregulation on morphine withdrawal behaviors and also permit to discard beta-adrenoceptor regulation as the neurochemical basis of the antiwithdrawal effect of yohimbine. The possible contribution of some other neurochemical effects of yohimbine are discussed to explain the inhibition of morphine dependence by that drug.     

Impaired nitric oxide synthase signaling dissociates social investigation and aggression.

A combination of social withdrawal and increased aggression is characteristic of several mental disorders. Most previous studies have investigated the neurochemical bases of social behavior and aggression independently, as opposed to how these behaviors are regulated in concert. Neuronal nitric oxide synthase (nNOS) produces gaseous nitric oxide, which functions as a neurotransmitter and is known to affect several types of behavior including mating and aggression. Compared with wild-type mice, we observed that nNOS knockout mice showed reduced behavioral responses to an intruder behind a wire barrier. Similar results were observed in mice treated with the selective nNOS inhibitor 3-bromo-7-nitroindazole (3BrN). In habituation-dishabituation tests, treatment with 3BrN did not block recognition of male urine but did attenuate investigation time compared with oil-treated animals. Finally, nNOS knockout mice and 3BrN treated mice were significantly more aggressive than wild-type and oil-treated males, respectively. In general, these behavioral effects are less pronounced in pair-housed males compared with singly-housed males. Thus, nNOS inhibition results in a phenotype that displays reduced social investigation and increased aggression. These data suggest that further study of nNOS signaling is warranted in mental disorders characterized by social withdrawal and increased aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Drinking by rats after lateral hypothalamic lesions: A new look at the lateral hypothalamic syndrome.

Rats that have recovered from aphagia and adipsia following lateral hypothalamic lesions are believed to be incapable of experiencing thirst and drink water simply to facilitate the consumption of dry food. However, the present results from adult Sprague-Dawley albino rats indicate that these Ss will drink in response to dehydration of the intracellular or intravascular fluid compartments and to hyperangiotensinemia, if testing continues beyond a few hours. Comparable effects also were obtained in Ss with mesencephalic brain damage, which appeared to destroy portions of the substantia nigra and the ascending nigrostriatal dopaminergic projections. These findings, when placed in the context of a recent neurochemical model for recovery of function, suggest a new interpretation of the lateral hypothalamic syndrome. (2 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased food intake, body weight, and adiposity in rats after regional neurochemical depletion of serotonin.

Assessed long-term changes in food and water intake, body weight (BW), and skeletal growth following bilateral hypothalamic microinfusions of 5,7-dihydroxytryptamine (DHT; 6 or 12 μg) in 16 female hooded rats. The analysis of ingestive behavior included assessment of photoperiodic effects and responsivity to alterations in dietary composition. The neuroanatomical and neurochemical selectivity of the serotonergic depletion was documented by regional spectrofluorometric analysis for serotonin (5-hydroxytryptamine, 5-HT), dopamine, and norepinephrine. Results indicate that, substantial depletion of 5-HT occurred in the septum, hippocampus, and hypothalamus of the DHT (12 μg) group. During feeding of a high-fat diet, the 5-HT-depleted Ss exhibited a long-lasting and stable hyperphagia that led to an increase in BW. Because BW increased in the absence of increased skeletal growth or intestinal weight, it is concluded that the increased BW reflected increased adiposity. Overall results provide evidence of an inhibitory role of 5-HT in food intake and point to the importance of maximizing both neurochemical and neuroanatomical selectivity. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exposure to slim images in mass media: Television commercials as reminders of restriction in restrained eaters.

Objective: The aim of the present study was to explore the effects of exposure to slim images and diet-related products in commercials on actual food intake in relation to dietary restraint. Design: An experimental design was used, in which food intake was measured in 124 female students who watched either a sad or a neutral movie on television, which was interrupted by either commercials featuring slim models and diet products, or neutral commercials. Subsequently, participants filled out questionnaires on dietary restraint and any tendency toward overeating. Main outcome variable: Intake of snack food while watching television. Results: It was found that highly restrained students exposed to commercials with slim models and diet-related products ate less food, whereas less restrained eaters ate slightly more after seeing these commercials. Conclusion: The findings suggest that restrained eaters confronted with diet products and slim images when watching television will be reminded of their restricted eating behavior and eat less. The present study provides support for the reinhibition theory of slim media images. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dopamine, effort, and decision making: Theoretical comment on Bardgett et al. (2009).

Forebrain dopamine (DA) systems are thought to be a critical component of the brain circuitry regulating behavioral activation, work output during instrumental behavior, and effort-related decision making. Tasks that offer animals choices between alternatives that require different degrees of effort can be used to assess effort-related choice behavior. Rats treated with DA antagonists, or with accumbens DA depletions, tend to show reduced selection of instrumental behaviors with high response requirements, and instead they choose to engage in food-seeking behaviors that involve less effort. The accompanying article by Bardgett et al. (see record 2009-04037-002) describes a novel effort-discounting task that involves the modification of a previously developed T-maze choice procedure (Salamone et al., 1994). Each arm of the maze contained different magnitudes of food reinforcement, and in order to obtain the higher magnitude reward, the rats had to climb a barrier in that arm of the maze. With training, rats were able to climb successively higher barriers to obtain the larger amount of food, and the choice between the high barrier arm and the no-barrier arm with the smaller reward served as a template for assessing the effects of dopaminergic drugs. D1 and D2 family antagonists, as well as the DA releasing agent amphetamine, were able to produce a bidirectional modulation of choice behavior, while drugs that act on D3 receptors were ineffective. These studies illustrate features of the neurochemical regulation of effort-related decision making, and may have implications for the understanding of both natural and pathological features of motivation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Emotional arousal and overeating in restrained eaters.

Tested the effects of 3 mood inductions (neutral, positive, and negative) on food intake in 91 women of varying degrees of dietary restraint. Mood induction was accomplished by exposure to 1 of 3 film segments: a travelogue (neutral affect), a comedy film (positive affect), and a horror film (negative affect). In Ss exposed to the neutral film, food intake decreased with increasing levels of dietary restraint. Among Ss who viewed either the comedy film or the horror film, however, food intake increased with increasing restraint. Although the horror film appeared to be more disinhibiting than the comedy film, this effect may have resulted from a difference in the intensity of the emotions induced rather than from their valence. These results suggest that emotional arousal, regardless of valence, may trigger overeating among restrained eaters. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Depression and stimulant dependence: neurobiology and pharmacotherapy

Depressive disorder rates in stimulant-dependent individuals are substantially higher than community rates. Further, depressive symptoms are considered a major component of stimulant withdrawal. The comorbidity of these disorders may reflect shared neurochemical alterations in the function of serotonin, dopamine, and peptide systems, such as corticotropin releasing factor (CRF) and neuropeptide Y (NPY). These alterations are observed in patients, and in animal models of depression and stimulant dependence, particularly in limbic brain structures. This shared neurobiology does not seem to result from significant shared heritability or genetic linkage; stimulants may induce changes in neurobiology that are similar to those found in depression, and these changes might provide a therapeutic target. Stimulant-dependent patients with a depressive disorder may be a specific subpopulation for antidepressant trials, and they might reduce their stimulant abuse when treated with antidepressants. Nevertheless, concomitant dependence on alcohol or opioids may influence this response, and antidepressants appear to be more effective for depression in combined stimulant and opioid dependence than in combined stimulant and alcohol dependence.     

Brain corticotropin-releasing factor mediates 'anxiety-like' behavior induced by cocaine withdrawal in rats

Anxiety is a key symptom of the cocaine withdrawal syndrome in human addicts, and it is considered to be one of the major factors in precipitating relapse to chronic cocaine abuse. Corticotropin-releasing factor (CRF) plays an important role in the pathophysiology of anxiety and depression, and it may also be involved in the acute behavioral and neuroendocrine actions of cocaine. The role of endogenous CRF in cocaine withdrawal-induced anxiety was investigated in the present study. Animals were subjected to chronic cocaine (20 mg/kg, intraperitoneally, once a day for 14 days) administration. Rats tested 30 min after the last cocaine injection did not show withdrawal anxiety on the elevated plus maze or any alterations in brain CRF levels. Withdrawal (48 h) from chronic cocaine administration produced an intense anxiety-like behavior characterized by decreased open arm exploration. Immunoreactive CRF (CRF-LI) levels were selectively altered in the hypothalamus, in the amygdala and in the basal forebrain structures at the time of the behavioral anxiety, reflecting an increased activity of brain CRF systems. Daily intracerebroventricular (i.c.v.) pretreatment with an immunoserum raised against CRF completely prevented the development of anxiety induced by cocaine withdrawal. These data suggest that extrahypothalamic-limbic CRF hypersecretion may be involved in the development of anxiety related to cocaine withdrawal and that the CRF system may be a useful target for new pharmacotherapies for cocaine withdrawal and relapse.     

Review of The organization of behavior: A neuropsychological theory.

Reviews the book, The organization of behavior: A neuropsychological theory by Donald O. Hebb (2002). Although scientists and philosophers had long speculated about the involvement of biological factors in psychological phenomena, it was not until the 20th century and the publication of The organization of behavior in 1949 that Physiological Psychology emerged as an active field of scientific research. The book also served as a launching pad for revolutionary developments in a wide range of other fields. What can be said to have emerged from the publication of this volume in 1949? Hebb had produced the first comprehensive theory about how brain activity might produce various complex psychological phenomena. The field of biopsychology did emerge and the widely held view that psychological functioning was too complex to have its roots in chemistry and physiology of the brain was discredited. His theorizing did stimulate transdisciplinary research. A significant number of biological scientists began to ask questions about the brain that were relevant to the understanding of psychological processes such as learning and memory. It also resulted in a change in the philosophic outlook of behavioural scientists. Models of thinking began to be built out of neurocircuits as scholars adopted a monistic position about mind and brain. Undergraduates and graduate students should be very grateful to Richard Brown and Peter Milner for their efforts in re-publishing this seminal book. The arguments outlined in the book remain just as compelling and transparent as they were 40 years ago. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Psychological testing and assessment in the 21st century.

As spin-offs of the current revolution in the cognitive and neurosciences, clinical neuropsychologists in the 21st century will be using biological tests of intelligence and cognition that record individual differences in brain functions at the neuromolecular, neurophysiologic, and neurochemical levels. Assessment of patients will focus more on better use of still intact functions, as well as rehabilitating or bypassing impaired functions, than on diagnosis, as is the focus today. Better developed successors to today's scales for assessing personal competency and adaptive behavior, as well as overall quality of life, also will be in wide use in clinical settings. With more normal individuals, use of new generations of paper-and-pencil inventories, as well as biological measures for assessing differences in interests, attitudes, personality styles, and predispositions, is predicted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neural mechanisms of tolerance to the effects of cocaine

Chronic use of cocaine in high doses can produce tolerance as assessed by various behavioral, neurochemical, cellular and molecular measures in specific brain regions. Tolerance to cocaine is indicated by drug discrimination and intracranial self-stimulation models, which show the development of tolerance after approximately 1 week of frequent cocaine treatment, with recovery after a similar period of cocaine abstinence. Tolerance to the reinforcing properties of cocaine depends on dose, duration and frequency of cocaine self-administered by experimental animal or human subjects. The mechanism underlying this effect may involve an absolute or relative attenuation of dopamine response to cocaine challenge after frequent or repeated treatment in the nucleus accumbens (NAc). Similarly, afferent and efferent NAc circuits exhibit reduced metabolic activity, which lasts throughout the early period of withdrawal following repeated treatment. Attenuation of immediate early gene response also occurs, which might be related to a functional desensitization of dopamine D1-like receptors. Furthermore, intracellular adaptive responses to chronic cocaine exposure induce striatal dynorphin expression decreasing the behavioral potency of subsequent drug treatment. Thus, a combination of various pharmacodynamic mechanisms and the attenuation of dopamine response induced by sufficient dose, duration and frequency of cocaine exposure ultimately invoke the transient development of tolerance to the reinforcing effects of cocaine.     

The neuropathogenesis of Borna disease virus infections

The unique genetic and biological properties of this small enveloped RNA virus indicate that Borna disease virus (BDV) is an evolutionary old pathogen. It appears perfectly adapted to persist inside the limbic system, a most delicate and sensitive old area of the mammalian brain involved in the control of mood, behavior, and memory. In many infected individuals, BDV remains a commensal during their lifetime. In a minority of vulnerable subjects, BDV becomes frequently activated, leading to episodes of distinct, more or less severe disturbances of information processing, behavioral and mood alterations. BDV research in humans is anticipated to initiate new insights into the interplay of exogenous and endogenous factors governing mood disorders. In nature BDV preferentially behaves as a neurotropic virus, but may latently and/or persistently infect cells of the reticuloendothelial system. This has been shown to be of great diagnostic importance, because now BDV 'footprints' can be followed in vivo in animals and man. BDV, which has long been considered as a classical animal virus, is present in humans, and has been found to be associated with some defined psychiatric disorders in particularly vulnerable individuals. An interaction of BDV proteins with neurotransmitter activities is plausible in the light of experimental animal data. Interference with normal behavior and the influence on mood and cognitive functions as demonstrated in animals and assumed in humans require extensive future research on the molecular etiopathogenesis. Aside from these clinical aspects, BDV is an unusual agent with outstanding features, namely replication in the nucleus of its target cells by an elusive, partially unknown mechanism, showing no cytopathogenicity or disturbance of vital cell functions, but altering luxury functions, and with a lifelong persistence giving rise to periods of long latency and short activation.