Brain Reward Centers Research Articles

The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives.

Mammals expend energy in many ways, including basic cellular maintenance and repair, digestion, thermoregulation, locomotion, growth and reproduction. These processes can vary tremendously among species and individuals, potentially leading to large variation in daily energy expenditure (DEE). Locomotor energy costs can be substantial for large-bodied species and those with high-activity lifestyles. For humans in industrialized societies, locomotion necessary for daily activities is often relatively low, so it has been presumed that activity energy expenditure and DEE are lower than in our ancestors. Whether this is true and has contributed to a rise in obesity is controversial. In humans, much attention has centered on spontaneous physical activity (SPA) or non-exercise activity thermogenesis (NEAT), the latter sometimes defined so broadly as to include all energy expended due to activity, exclusive of volitional exercise. Given that most people in Western societies engage in little voluntary exercise, increasing NEAT may be an effective way to maintain DEE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviours (e.g. watching television). The effects of voluntary exercise on other components of physical activity are highly variable in humans, partly as a function of age, and have rarely been studied in rodents. However, most rodent studies indicate that food consumption increases in the presence of wheels; therefore, other aspects of physical activity are not reduced enough to compensate for the energetic cost of wheel running. Most rodent studies also show negative effects of wheel access on body fat, especially in males. Sedentary behaviours per se have not been studied in rodents in relation to obesity. Several lines of evidence demonstrate the important role of dopamine, in addition to other neural signaling networks (e.g. the endocannabinoid system), in the control of voluntary exercise. A largely separate literature points to a key role for orexins in SPA and NEAT. Brain reward centers are involved in both types of physical activities and eating behaviours, likely leading to complex interactions. Moreover, voluntary exercise and, possibly, eating can be addictive. A growing body of research considers the relationships between personality traits and physical activity, appetite, obesity and other aspects of physical and mental health. Future studies should explore the neurobiology, endocrinology and genetics of physical activity and sedentary behaviour by examining key brain areas, neurotransmitters and hormones involved in motivation, reward and/or the regulation of energy balance.

Reputation for reciprocity engages the brain reward center

Brain reward circuitry, including ventral striatum and orbitofrontal cortex, has been independently implicated in preferences for fair and cooperative outcomes as well as learning of reputations. Using functional MRI (fMRI) and a "trust game" task involving iterative exchanges with fictive partners who acquire different reputations for reciprocity, we measured brain responses in 36 healthy adults when positive actions (entrust investment to partners) yield positive returns (reciprocity) and how these brain responses are modulated by partner reputation for repayment. Here we show that positive reciprocity robustly engages the ventral striatum and orbitofrontal cortex. Moreover, this signal of reciprocity in the ventral striatum appears selectively in response to partners who have consistently returned the investment (e.g., a reputation for reciprocity) and is absent for partners who lack a reputation for reciprocity. These findings elucidate a fundamental brain mechanism, via reward-related neural substrates, by which human cooperative relationships are initiated and sustained.

Brain Region's Dopamine Levels Linked to Psychopathy Trait

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessBrain Region's Dopamine Levels Linked to Psychopathy TraitJoan Arehart-TreichelJoan Arehart-TreichelSearch for more papers by this authorPublished Online:7 May 2010https://doi.org/10.1176/pn.45.9.psychnews_45_9_022AbstractAh, the “bad guy” is thinking, “I'm going to take that sucker for all he's worth.”An overly responsive nucleus accumbens—illustrated in this brain image—may prompt antisocial individuals to be aggressive.Credit: Gregory Samanez-Larkin and Joshua Buckholtz, Vanderbilt UniversityWhat's going on in his brain? His brain's reward center—the nucleus accumbens—may be goading him into action, a new study suggests.The study found a link between the personality trait of psychopathy and an overly responsive nucleus accumbens.Joshua Buckholtz, a doctoral candidate in neuroscience at Vanderbilt University, headed the study. Results were reported online March 14 in Nature Neuroscience.The personality trait of psychopathy is characterized by charm, egocentricity, manipulation of others, sensation-seeking, poor reflection, and blunted empathy. Psychopathy in turn is a robust predictor of antisocial behavior.Moreover, alcohol, nicotine, and many other drugs of abuse are known to stimulate the nucleus accumbens, and psychopathic individuals are known to be at heightened risk for developing substance abuse problems. So Buckholtz and his colleagues suspected that there might be a link between the personality trait of psychopathy and the nucleus accumbens. They conducted a study to find out.They recruited 24 community volunteers and used the Psychopathic Personality Inventory, a validated measurement of psychopathy, to determine how each subject scored on a subdomain of the trait called “impulsive antisociality.” This subdomain in turn has been linked with antisocial behavior, aggression, impulsivity, and substance abuse both in prison and community samples.In a first experiment, the subjects were given an amphetamine, which is known to increase levels of the neurotransmitter dopamine in the nucleus accumbens. After that, PET scans were used to measure the amount of dopamine released in the nucleus accumbens of each subject. The researchers looked to see whether there was any correlation between how high subjects had scored on impulsive antisociality and the amount of dopamine released in their nucleus accumbens.The higher subjects had scored on impulsive antisociality, the more dopamine they released. In fact, when the highest-scoring subjects were compared with the lowest-scoring ones, the former released four times more dopamine in the nucleus accumbens than the latter did.In a second experiment, the subjects played a game in which they could win a cash reward. While they were playing the game, fMRI scans were used to see how much dopamine was released in their nucleus accumbens. The higher subjects had scored on impulsive antisociality, the more dopamine they released.So the combined results from both experiments appear to indicate that people who score high on impulsive antisociality possess an especially responsive nucleus accumbens, or reward system.But what do these findings mean in practical terms? One possibility is that people with an especially responsive reward system might be aggressive about obtaining whatever they consider rewarding, whether it is drugs, sex, money, or something else. Indeed, rodent studies have shown that dopamine is released from the nucleus accumbens during aggressive behavior, and aggressive behavior is common among antisocial or psychopathic individuals.Although Buckholtz and his group believe that they've taken an important first step in linking impulsive antisociality to an exaggerated dopamine response in the nucleus accumbens, they now hope to confirm their results in subjects who have been diagnosed as having antisocial personality disorder.And if they manage to do so, then an especially responsive reward system might be considered one of the biological hallmarks of antisocial individuals, just as deficits in the prefrontal cortex and amygdala already are (Psychiatric News, April 5, 2002; October 16, 2009).The study was funded by the National Institute on Drug Abuse.An abstract of “Mesolimbic Dopamine Reward System Hypersensitivity in Individuals With Psychopathic Traits” is posted at <www.nature.com/neurojournal/vaop/ncurrent/pdf/nn.2510.pdf>. ISSUES NewArchived

β-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats

We investigated the short- and long-term effects of ceftriaxone on glutamate transporter subtype 1 (GLT-1) transporter activity and extracellular glutamate in the rat nucleus accumbens. Repeated ceftriaxone administration (50, 100 or 200 mg/kg, i.p.) produced a dose-dependent reduction in glutamate levels that persisted for 20 days following discontinuation of drug exposure. The ceftriaxone effect was prevented by the GLT-1 transporter inhibitor dihydrokainate (1 μM, intra-accumbal). These results suggest that β-lactam antibiotics produce an enduring reduction in glutamatergic transmission in the brain reward center.

Normalizing Effects of Modafinil on Cocaine-Induced Sleep Abnormalities

Normalizing Effects of Modafinil on Cocaine-Induced Sleep Abnormalities

Optimal Waist-to-Hip Ratios in Women Activate Neural Reward Centers in Men

Secondary sexual characteristics convey information about reproductive potential. In the same way that facial symmetry and masculinity, and shoulder-to-hip ratio convey information about reproductive/genetic quality in males, waist-to-hip-ratio (WHR) is a phenotypic cue to fertility, fecundity, neurodevelopmental resources in offspring, and overall health, and is indicative of “good genes” in women. Here, using fMRI, we found that males show activation in brain reward centers in response to naked female bodies when surgically altered to express an optimal (∼0.7) WHR with redistributed body fat, but relatively unaffected body mass index (BMI). Relative to presurgical bodies, brain activation to postsurgical bodies was observed in bilateral orbital frontal cortex. While changes in BMI only revealed activation in visual brain substrates, changes in WHR revealed activation in the anterior cingulate cortex, an area associated with reward processing and decision-making. When regressing ratings of attractiveness on brain activation, we observed activation in forebrain substrates, notably the nucleus accumbens, a forebrain nucleus highly involved in reward processes. These findings suggest that an hourglass figure (i.e., an optimal WHR) activates brain centers that drive appetitive sociality/attention toward females that represent the highest-quality reproductive partners. This is the first description of a neural correlate implicating WHR as a putative honest biological signal of female reproductive viability and its effects on men's neurological processing.

Grief and Depression: Treatment Decisions for Bereaved Children and Adults

Grief and Depression: Treatment Decisions for Bereaved Children and Adults

Understanding of nicotinic acetylcholine receptors

Understanding of nicotinic acetylcholine receptors

Lasting Reduction of Cocaine Action in Neostriatum— A Hydrolase Gene Therapy Approach

We previously found that a quadruple mutant cocaine hydrolase derived from human butyrylcholinesterase [termed cocaine esterase (CocE)] can suppress or reverse cocaine toxicity and abolish drug-primed reinstatement in rats. Here, we examined whether gene transfer of CocE reduces cocaine actions in brain reward centers. Early experiments used a standard, early region 1-deleted adenoviral vector, which, after intravenous delivery of 10(10) plaque-forming units, caused plasma cocaine hydrolase activity to rise 25,000-fold between day 4 and day 7. During this period, under a protocol that typically induces FosB expression in the caudate nucleus, these rats and unprotected controls given only empty vector or saline were subjected to repeated twice-daily injections of cocaine (30 mg/kg i.p.). Immunohistochemistry of the neostriatum on day 7 showed many FosB-reactive nuclei in unprotected rats but few if any in rats pretreated with active vector, which resembled rats never exposed to cocaine. Western blots confirmed this result. In contrast there was a more localized protection against cocaine-elicited FosB induction when hydrolase vector was injected directly into the ventral striatum, which generated high transgene expression in many neurons of the target area. Similar results were obtained with systemic and local injection of a more efficient helper-dependent adenoviral vector, which transduced high levels of hydrolase for at least 2 months, with lesser expression continued up to 1 year. Behavioral tests are now warranted to determine whether such effects can reduce drug-seeking behavior and lower the probability of relapse.

Activation in brain energy regulation and reward centers by food cues varies with choice of visual stimulus

ObjectiveTo develop a noninvasive method of studying brain mechanisms involved in energy homeostasis and appetite regulation in humans by using visual food cues that are relevant to individuals attempting weight loss.DesignFunctional magnetic resonance imaging (fMRI) was used to compare brain activation in regions of interest between groups of food photographs.Participants10 healthy, nonobese women who were not dieting for weight loss.MeasurementsIndependent raters viewed food photographs and evaluated whether the foods depicted should be eaten by individuals attempting a calorically-restricted diet. Based on their responses, we categorized photographs into “non-fattening” and “fattening” food groups, the latter characterized by obviously high caloric content and usually also high fat or high sugar content. Blood oxygen level-dependent (BOLD) response was measured by fMRI while participants viewed photographs of “fattening” foods, “non-fattening” foods, and non-food objects.ResultsViewing photographs of fattening food compared to non-food objects resulted in significantly greater activation in the brainstem; hypothalamus; left amygdala; left dorsolateral prefrontal cortex; left orbitofrontal cortex; right insular cortex; bilateral striatum, including the nucleus accumbens, caudate nucleus, and putamen; bilateral thalamus; and occipital lobe. By comparison, only the occipital region had greater activation by non-fattening food than by object photographs. Combining responses to all food types resulted in attenuation of activation in the brainstem, hypothalamus, and striatum.ConclusionThese findings suggest that, in nonobese women, neural circuits engaged in energy homeostasis and reward processing are selectively attuned to representations of high-calorie foods that are perceived as fattening. Studies to investigate hormonal action or manipulation of energy balance may benefit from fMRI protocols that contrast energy-rich food stimuli with non-food or low-calorie food stimuli.

Internet Sex Addiction Treated With Naltrexone

Internet Sex Addiction Treated With Naltrexone

Internet Sex Addiction Treated With Naltrexone

Malfunctioning of the brain's reward center is increasingly understood to underlie all addictive behavior. Composed of mesolimbic incentive salience circuitry, the reward center governs all behavior in which motivation has a central role, including acquiring food, nurturing young, and having sex. To the detriment of normal functioning, basic survival activities can pale in importance when challenged by the allure of addictive substances or behaviors. Dopamine is the neurotransmitter driving both normal and addictive behavior. Other neurotransmitters modulate the amount of dopamine released in response to a stimulus, with the salience determined by the intensity of the dopamine pulse. Opiates (either endogenous or exogenous) exemplify such modulators. Prescribed for treating alcoholism, naltrexone blocks opiates' capacity to augment dopamine release. This article reviews naltrexone's mechanism of action in the reward center and describes a novel use for naltrexone in suppressing a euphorically compulsive and interpersonally devastating addiction to Internet pornography.

Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens

Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology – thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes – in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.

Choosing the right medication for the treatment of alcoholism

In the past decade, scientists have made important progress toward understanding the neurobiology underlying an alcohol disorder. This knowledge has led to the development of promising pharmacotherapies that target the neural pathways involved in the brain's reward center in such a way that the usual treatment response (via counseling) is substantially improved upon. There are now four US Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of alcohol dependence: disulfiram (Antabuse; Odyssey Pharmaceuticals, East Hanover, NJ), oral naltrexone (ReVia; Barr Pharmaceuticals, Inc., Pomona, NY), acamprosate (Campral; Forest Laboratories, Inc., New York, NY), and, as of April 2006, an extended-release (30-day) injectable suspension formulation of naltrexone (Vivitrol; Alkermes, Inc., Cambridge, MA). Other types of medications (eg, topiramate and quetiapine) are currently under investigation for the treatment of alcohol dependence. Research also has provided insights into best practices for prescribing the available medications. This report reviews the latest innovations in pharmacotherapy for the treatment of alcohol dependence, focusing on FDA-approved medications presently available to the treatment community.

Aquaporin-4 knockout regulated cocaine-induced behavior and neurochemical changes in mice

Aquaporin-4 (AQP4) is the predominant water channel of brain, which mediates transmembrane water movement at the blood–brain barrier and at the brain–cerebrospinal fluid interface. It has been reported that AQP4 deletion results in an increase of amino acid and monoamine levels in some brain regions of mice, suggesting that AQP4 may participate in region-specific alterations in brain amino acid and monoamine metabolism. In the present study, we examined whether AQP4 affects neurotransmission in acute and chronic cocaine exposure mice. For this purpose, both wild-type and AQP4 knockout mice were used with locomotor activity evaluation and microdialysis methods. The results reveal that AQP4 deletion attenuated locomotor activity in acute and repeated cocaine exposure mice, and induced a decrease of extracellular dopamine and glutamate levels in the nucleus accumbens (NAc), a brain region known to be critically involved in the addictive properties of cocaine. Therefore, AQP4 may play a role in regulating extracellular cocaine-induced dopamine and glutamate release in the brain reward center, and in turn AQP4 deletion may attenuate cocaine reinforcement and dependence.

Iptakalim inhibits nicotine-induced enhancement of extracellular dopamine and glutamate levels in the nucleus accumbens of rats

Iptakalim (Ipt) is a novel ATP-sensitive potassium channel opener. It has been reported that Ipt inhibited cocaine-induced dopamine and glutamate release, suggesting that Ipt may regulate drug addiction. Recently, we found that Ipt blocked nicotinic acetylcholine receptor (nAChR)-mediated currents in a heterologously expressed SH-EP1 cell line and in native midbrain dopamine neurons. In the present study, we examined whether Ipt prevents nicotine-induced neurotransmitter release in the nucleus accumbens (NAc) using in vivo microdialysis methods in awake, freely moving rats. Ipt was administered through a microdialysis probe, following systemic administration of nicotine (0.5 mg/kg, s.c.). The results show that acute nicotine treatment induced an increase of both dopamine and glutamate levels in the rat NAc, and that Ipt significantly attenuated nicotine's effects in a concentration-dependent manner. Therefore, Ipt may serve as a novel compound to block nicotine-induced dopamine and glutamate release in the brain reward center, in turn decreasing nicotine reinforcement and dependence.

Cocaine dependence: a disease of the brain's reward centers.

Cocaine addiction affects brain reward centers that have evolved to ensure survival. Cocaine euphoria is intensely pleasurable and results from mesolimbic dopamine (DA) neurotransmission. DA signal-receiving neurons in the nucleus accumbens synthesize endogenous opioids and project to numerous reward regions. Cocaine-induced neuroadaptations, including DA depletion, may underlie craving and hedonic dysregulation. Cue-induced craving is vigorously triggered by conditioned elements of the drug environment and associated with measurable limbic activation. Reduced frontal lobe metabolism in cocaine-addicted individuals could explain important clinical phenomena such as denial and the loss of control over limbic impulses. Cocaine addiction is rapidly progressive and associated with severe medical, psychiatric, and psychosocial consequences. Denial shields addicted individuals from their predicament and must be addressed in treatment. Lacking pharmacological options, clinicians must rely entirely on psychosocial approaches. Treatment principles, including engagement, motivational enhancement, abstinence strategies, and craving reduction are discussed in terms of biological rationales.

Differential Susceptibility to Comorbid Drug Abuse and Violence

Although many psychoactive substances have been associated with violent behavior, only a subgroup manifests excessively aggressive behavior when sober or intoxicated. Theories to explain addictive behaviors in general may directly relate to the specific proclivity to exhibit excessive aggression in this subset of users. Certain personality traits and cognitive deficits coexist in individuals prone to both drug abuse and violence, suggesting a common origin. Because these excessive and compulsive behaviors have been linked with aberrations in the metabolism and activity of the neurotransmitters dopamine and serotonin, their origins may be partly genetic or biological. Alterations in neurotransmitter function influence activities within the brain's reward center to perturb nervous system arousal levels, thereby increasing stimulation-seeking behaviors. Manifestations of these neurobiological aberrations can be measured in physiological and biochemical processes that serve to mediate these behavioral and psychological outcomes.

Neurochemistry and sexual addiction

Abstract Sexual addiction is presented as a manifestation of altered neuro-chemistry brought about by behavioral excess. Neurochemical changes in the brain's reward center that accompany cocaine abuse are compared to those endured by the sexual addict. The accepted model of neuroadaptation for drug dependence is utilized as the foundation for the authors' thesis that sexual addiction, although more complex than drug addiction, is not fundamentally different.

Addictiveness of Central Stimulants

Central stimulants have been abused since their inception and we are currently in the midst of a cocaine epidemic that challenges our resources and capabilities. Through their actions on powerful endogenous reward centers, central stimulants produce intense euphoria that reinforces subsequent usage and eventual dependence. Considerable evidence indicates that the activation of dopamine circuits mediates stimulant reward. With regard to cocaine, it has been hypothesized that depletion of central dopamine leads to craving. Euphoria and craving, the key dynamics of stimulant addiction, may therefore result largely from neurochemical alterations of dopamine systems in the brain's reward center. Progressive deterioration of the stimulant addict involving medical, psychiatric, and psychosocial impairment occurs rapidly, underscoring the addiction potential of these agents. Tolerance, sensitization and withdrawal phenomena are discussed from clinical and neurochemical perspectives.