Subordinate Monkeys Research Articles

Social Information Signaling by Neurons in Primate Striatum

Social decisions depend on reliable information about others. Consequently, social primates are motivated to acquire information about the identity, social status, and reproductive quality of others. Neurophysiological and neuroimaging studies implicate the striatum in the motivational control of behavior. Neuroimaging studies specifically implicate the ventromedial striatum in signaling motivational aspects of social interaction. Despite this evidence, precisely how striatal neurons encode social information remains unknown. Therefore, we probed the activity of single striatal neurons in monkeys choosing between visual social information at the potential expense of fluid reward. We show for the first time that a population of neurons located primarily in medial striatum selectively signals social information. Surprisingly, representation of social information was unrelated to simultaneously expressed social preferences. A largely nonoverlapping population of neurons that was not restricted to the medial striatum signaled information about fluid reward. Our findings demonstrate that information about social context and nutritive reward are maintained largely independently in striatum, even when both influence decisions to execute a single action.

Social stress interacts with diet history to promote emotional feeding in females

Stress-induced eating disorders cause significant health problems and are often co-morbid with mood disorders. Emotional feeding, particularly in women, may be important for the development of obesity and failed attempts to lose weight. However, prospective studies assessing the effect of chronic psychosocial stress on appetite in different dietary environments in females are lacking. The present study tested the hypothesis that chronic psychosocial stress would increase consumption of high caloric diet and this emotional feeding would persist even when a healthier diet was available. Socially housed female rhesus monkeys were studied to address whether subordination increases caloric intake when a high fat and sugar diet (HFSD) was available concurrently with a low fat, high fiber diet (LCD). Cortisol responsivity and food intake were quantified during this choice phase and when only the LCD was available. The order of diet condition was counterbalanced to assess whether a history of HFSD would affect appetite. All females preferred the HFSD but subordinates consumed significantly more calories during the choice phase. The increased calorie intake was maintained in subordinate monkeys even after withdrawal of the HFSD. Subordinate females demonstrated reduced glucocorticoid negative feedback, with post dexamethasone serum cortisol levels significantly predicting intake of the HFSD but not the LCD during the choice condition. The cortisol response to an acute stressor significantly predicted subsequent intake of a HFSD in all females. Continual exposure to the psychosocial stress of subordination in female monkeys results in excess caloric intake of foods that mimic a western dietary environment. In addition, this social stressor interacts with a history of HFSD intake to promote increased feeding even in a healthy dietary environment.

Modeling depression in adult female cynomolgus monkeys (Macaca fascicularis)

Depressive disorders are prevalent, costly, and poorly understood. Male rodents in stress paradigms are most commonly used as animal models, despite the two-fold increased prevalence of depression in women and sex differences in response to stress. Although these models have provided valuable insights, new models are needed to move the field forward. Social stress-associated behavioral depression in adult female cynomolgus macaques closely resembles human depression in physiological, neurobiological, and behavioral characteristics, including reduced body mass, hypothalamic-pituitary-adrenal axis perturbations, autonomic dysfunction, increased cardiovascular disease risk, reduced hippocampal volume, altered serotonergic function, decreased activity levels, and increased mortality. In addition, behaviorally depressed monkeys also have low ovarian steroid concentrations, even though they continue to have menstrual cycles. Although this type of ovarian dysfunction has not been reported in depressed women and is difficult to identify, it may be the key to understanding the high prevalence of depression in women. Depressive behavior in female cynomolgus monkeys is naturally occurring and not induced by experimental manipulation. Different social environmental challenges, including isolation vs. subordination, may elicit the depression-like response in some animals and not others. Similarly, social subordination is stressful and depressive behavior is more common in socially subordinate monkeys. Yet, not all subordinates exhibit behavioral depression, suggesting individual differences in sensitivity to specific environmental stressors and enhanced risk of behavioral depression in some individuals. The behavior and neurobiology of subordinates is distinctly different than that of behaviorally depressed monkeys, which affords the opportunity to differentiate between stressed and depressed states. Thus, behaviorally depressed monkeys exhibit numerous physiological, neurobiological, and behavioral characteristics same as those of depressed human beings. The nonhuman primate model represents a new animal model of depression with great promise for furthering our understanding of this prevalent and debilitating disease and identifying novel therapeutic targets.

Erratum to: Increased ghrelin sensitivity and calorie consumption in subordinate monkeys is affected by short-term astressin B administration

Erratum to: Increased ghrelin sensitivity and calorie consumption in subordinate monkeys is affected by short-term astressin B administration

Impairment of ovarian function and associated health-related abnormalities are attributable to low social status in premenopausal monkeys and not mitigated by a high-isoflavone soy diet.

Psychological stress may impair premenopausal ovarian function and contribute to risk for chronic disease. Soy isoflavones may also influence ovarian function and affect health. Here, we report the effects of a psychological stressor (subordinate social status) and dietary soy on reproductive function and related health indices in female monkeys. We hypothesized that reproductive compromise and adverse health outcomes would be induced in subordinate when compared with dominant monkeys and be mitigated by exposure to soy. Subjects were 95 adult cynomolgus monkeys (Macaca fascicularis) housed in social groups of five or six. Animals consumed a soy-free, animal protein-based diet during an 8-month Baseline phase and then, during a 32-month Treatment phase, consumed either the baseline diet or an identical diet that substituted high-isoflavone soy protein for animal protein. Across more than 1200 menstrual cycles, subordinate monkeys consistently exhibited ovarian impairment [increased cycle length (P < 0.02) and variability (P < 0.02) and reduced levels of progesterone (P < 0.04) and estradiol (P < 0.04)]. Subordinate status was confirmed behaviorally and was associated with elevated cortisol (P < 0.04) and relative osteopenia (P < 0.05). Consumption of the soy diet had no significant effects. (i) Psychological stress adversely affects ovarian function and related health indices in a well-accepted animal model of women's health; (ii) Similar effects may extend to women experiencing reproductive impairment of psychogenic origin; (iii) soy protein and isoflavones neither exacerbate nor mitigate the effects of an adverse psychosocial environment; and (iv) this study was limited by an inability to investigate the genetic and developmental determinants of social status.

Increased ghrelin sensitivity and calorie consumption in subordinate monkeys is affected by short-term astressin B administration

Animals chronically exposed to stressors with access to diets high in fat and sugar consume and prefer these diets, a result consistent with the association between stress and comfort food ingestion in humans. As social subordination in rhesus monkeys provides an ethologically relevant translational model of psychosocial stress, we tested the hypothesis that differences in food intake between dominant and subordinate female monkeys are due to corticotropin-releasing hormone-(CRH) induced alteration in sensitivity to ghrelin, a potent orexigenic signal. We assessed food intake of animals given a choice between a low (LCD) and high calorie diet (HCD) in response to 4-day treatment with the CRH receptor antagonist, astressin B, and to an acute treatment of ghrelin. Ghrelin stimulated intake of LCD in subordinates but did not further increase consumption of HCD, whereas ghrelin decreased LCD consumption without affecting HCD intake in dominant females. Astressin B decreased cortisol levels and increased preference for and intake of the HCD in subordinates and decreased calorie intake and HCD preference in dominant animals. These results suggest that increased caloric intake by subordinates may, in part, be explained by a greater sensitivity to postprandial increases in ghrelin and that CRH receptor antagonism leading to a decrease in cortisol has mixed effects on food choice depending on an individual's stress background.

Effects of chronic administration of dopamine D2‐like receptor agonists aripiprazole and (−)‐N‐propyl‐norapomorphine on food/cocaine choice in socially housed monkeys

Dopamine D2‐like receptor partial agonists have been suggested as treatments for substance abuse. The goal of this study was to characterize the effects of D2‐like receptor agonists on the relative reinforcing strength of cocaine using a food‐drug choice procedure in socially housed cynomolgus monkeys. In daily self‐administration sessions, monkeys chose between food pellets and cocaine injections (0.003–0.1 mg/kg). The available cocaine dose increased during the session to generate a full dose‐effect curve each day. The high‐efficacy agonist (−)‐N‐propyl‐norapomorphine [(−)‐NPA; 0.001–0.0056 mg/kg] or the lower‐efficacy agonist aripiprazole (ARI; 0.01–0.1 mg/kg) was administered for 5 days; self‐administration was examined on Day 1 and Day 5. At least one ARI dose decreased cocaine choice in most dominant monkeys, but did not affect or increased cocaine choice in subordinates. In contrast, (−)NPA was more effective in decreasing cocaine choice in subordinate monkeys, although increases in cocaine choice were observed in most monkeys. Tolerance was rarely observed across days; in general effects of both drugs were maintained or exacerbated over 5 days. Results suggest that ARI and (−)‐NPA produce qualitatively different effects on the reinforcing strength of cocaine, perhaps due to differing intrinsic efficacies, and that the effects are modulated by social rank. Support: DA12460, DA10584.

Differences in D2 dopamine receptor availability and reaction to novelty in socially housed male monkeys during abstinence from cocaine

Studies in socially housed monkeys have demonstrated an influence of position in the social dominance hierarchy on brain dopamine D2 receptors and the reinforcing effects of cocaine that dissipates after long-term cocaine self-administration. The aims of the study were to examine the effects of abstinence from cocaine on D2 receptors in socially housed monkeys and to extend behavioral characterizations to measures of reactivity to a novel object. Twelve socially housed male cynomolgus monkeys with extensive cocaine self-administration experience were used (average lifetime intakes ∼270 and 215 mg/kg for dominant and subordinate monkeys, respectively). Abstinence lasted for approximately 8 months, after which D2 receptor availability was assessed using positron emission tomography and the D2 ligand [18F]fluoroclebopride. Reaction to novelty was also assessed in these subjects as well as nine individually housed monkeys. During abstinence, D2 receptor availability in the caudate nucleus was significantly higher in dominant versus subordinate monkeys. Average latency to touch a novel object was also significantly higher in dominant monkeys compared to subordinates or individually housed monkeys. In socially experienced monkeys, a significant positive correlation was observed between caudate nucleus D2 receptor availability and latencies to touch the novel object. Although chronic cocaine self-administration blunts the ability of social dominance to alter D2 receptor availability and sensitivity to the reinforcing effects of cocaine, this influence reemerges during abstinence. In addition, the data suggest that prior experience with social dominance can lead to longer latencies in reaction to novelty--a personality trait associated with low vulnerability to cocaine abuse.

Social intelligence in tufted capuchin monkeys

Tufted capuchin monkeys (Cebus apella), a species of New World primates, are known to be adept at various complex tool use both in the laboratory and in the wild. With their manual dexterity, they work as a helper for quadriplegic people. Social intelligence hypothesis, which places social intelligence as a major factor to advance complex information processing capability, predicts advanced social intelligence in this species with highly developed physical intelligence. In this paper, I describe a series of studies on social intelligence of this species in our comparative cognition laboratory at Kyoto University. As a competitive aspect of social intelligence, we analyzed spontaneous deceptive behavior between the monkeys. Two monkeys, dominant and subordinate, faced each other in the transparent boxes and two food cups were placed between them. When the subordinate monkey opened the baited cup, the dominant opponent was able to usurp the food. Some of the subordinates started to open the empty cup first: a behavior that could be interpreted as a deceptive act. As a cooperative aspect, we showed that two monkeys cooperated by dividing a sequence of behavior necessary to obtain rewards. This behavior continued even when only one of the participants received a reward if their roles were switched every trial; a reciprocal altruism was shown. To examine whether such complicated social behaviors reflect processes of mentalizing, we asked whether capuchin monkeys have cognitive components underlying them. We found that the monkeys are capable of recognizing attentional states of humans, inferring consequences of other's behavior, recognizing other's knowledge status, inferring the cause of other's emotional expression, and recognizing other's welfare. Thus these primitive aspects of mentalizing are clearly shared in species that is much more distant from humans than apes.

Relationship between social rank and cortisol and testosterone concentrations in male cynomolgus monkeys (Macaca fascicularis).

In nonhuman primate social groups, biological differences related to social status have proven useful for investigating the mechanisms of sensitivity to various disease states. Physiological and neurobiological differences between dominant and subordinate monkeys have been interpreted in the context of chronic social stress. The present experiments were designed to investigate the relationships between basal cortisol and testosterone concentrations and the establishment and maintenance of the social hierarchy in male cynomolgus monkeys. Cortisol concentrations were measured at baseline and following suppression with dexamethasone (DEX) and subsequent administration of adrenocorticotrophic hormone (ACTH) while monkeys were individually housed (n = 20) and after 3 months of social housing (n = 4/group), by which time dominance hierarchies had stabilised. Cortisol was also measured during the initial 3 days of social housing. Neither pre-social housing hormone concentrations, nor hypothalamic-pituitary-adrenal (HPA) axis sensitivity predicted eventual social rank. During initial social housing, cortisol concentrations were significantly higher in monkeys that eventually became subordinate; this effect dissipated within 3 days. During the 12 weeks of social housing, aggressive and submissive behaviours were observed consistently, forming the basis for assignment of social ranks. At this time, basal testosterone and cortisol concentrations were significantly higher in dominant monkeys and, after DEX suppression, cortisol release in response to a challenge injection of ACTH was significantly greater in subordinates. These results indicate that basal cortisol and testosterone concentrations and HPA axis function are state variables that differentially reflect position in the dominance hierarchy, rather than trait variables that predict future social status.

Behavioral and neurobiological characteristics influencing social hierarchy formation in female cynomolgus monkeys

Socially housed monkeys have been used as a model to study human diseases. The present study examined behavioral, physiological and neurochemical measures as predictors of social rank in 16 experimentally naïve, individually housed female cynomolgus monkeys (Macaca fascicularis). The two behavioral measures examined were novel object reactivity (NOR), as determined by latency to touch an opaque acrylic box placed in the home cage, and locomotor activity assessed in a novel open-field apparatus. Serum cortisol concentrations were evaluated three times per week for four consecutive weeks, and stress reactivity was assessed on one occasion by evaluating the cortisol response to adrenocorticotropic hormone (ACTH) following dexamethasone suppression. Measures of serotonin (5-HT) function included whole blood 5-HT (WBS) concentrations, cerebrospinal fluid (CSF) concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) and brain 5-HT transporter (SERT) availability obtained using positron emission tomography (PET). After baseline measures were obtained, monkeys were assigned to four social groups of four monkeys per group. The two measures that correlated with eventual social rank were CSF 5-HIAA concentrations, which were significantly higher in the animals who eventually became subordinate, and latency to touch the novel object, which was significantly lower in eventual subordinate monkeys. Measures of 5-HT function did not change as a consequence of social rank. These data suggest that levels of central 5-HIAA and measures of novel object reactivity may be trait markers that influence eventual social rank in female macaques.

Review. Positron emission tomography imaging studies of dopamine receptors in primate models of addiction.

Animal models have provided valuable information related to trait and state variables associated with vulnerability to drug addiction. Our brain imaging studies in monkeys have implicated D2 receptors in cocaine addiction. For example, an inverse relationship between D2 receptor availability and rates of cocaine self-administration has been documented. Moreover, environmental variables, such as those associated with formation of the social hierarchy, can impact receptor availability and sensitivity to the abuse-related effects of cocaine. Similarly, both D2 receptor availability and cocaine self-administration can be altered by chronic drug administration and fluctuations in hormone levels. In addition, cocaine self-administration can be altered in an orderly fashion by presentation of an acute stressor, such as acting as an intruder into an unfamiliar social group, which can shift the cocaine dose-response curve to the left in subordinate monkeys and to the right in dominant animals, suggesting an interaction between social variables and acute stressors. Conversely, irrespective of social rank, acute environmental enrichment, such as increasing the size of the living space, shifts the cocaine dose-response curve to the right. These findings highlight a pervasive influence of the environment in modifying the reinforcing effects of cocaine and strongly implicate brain D2 receptors.

Dario Maestripieri: Macachiavellian Intelligence. How Rhesus Macaques and Humans Have Conquered the World

Maestripieri has written for a popular audience, using the rhesus monkey as an animal model to understand humans. Although he uses cognitive terms to explain human and macaque behavior, for the monkey he explains that the function has been selected for and that no conscious awareness is implied. The description of subordinate monkeys seeking power to revenge the “harassment” and “humiliation” that they have suffered, suggests that he also uses a human model to understand monkeys. Even the clever title reveals the use of a human model to understand rhesus behavior. It is easy to forget the warnings against presuming conscious awareness in monkeys when he writes “...mothers are already thinking about their next infants and reducing their investment in the current ones” (P.118) or that infants “feign illness” and get into trouble to “blackmail” their mothers. Explaining vigorous infant sucking as a means of delaying mother returning to cycling is as enlightening as saying that a carpenter hammers nails in order to develop calluses on his/her hand. In the process of explaining rhesus and human behavior Maestripieri also shares much of his personal history. Maestripieri believes that males are always motivated by sex and females trade sex for tolerance, support etc. He uses an economic model to explain behavior, and certainly natural selection favors actions where the benefit outweighs the costs, but although he says that rhesus are “good accountants,” I doubt that rhesus keep track of costs and benefits to decide what to do to whom. I too have studied rhesus monkeys, but I am more of an iconoclast than Maestripieri. It may be reasonable for an alpha male to mate with as many females as possible while deterring other males from doing the same, but then why do alpha males take so many mounts to ejaculate, while subordinates do so in one or two? Tom Gordon once witnessed every copulation in a group during the season and found that although the number of

Effects of acute stress and environmental enrichment on cocaine self‐administration in socially housed monkeys

Previous research has shown that social rank can influence the reinforcing effects of cocaine in monkeys (Morgan et al. 2002; Czoty et al. 2005). It has been hypothesized that dominant and subordinate monkeys represent a continuum from environmental enrichment to socially‐derived stress. Whereas social rank reflects a chronic condition, the effects of additional enrichment or stress on cocaine self‐administration (SA) has not been examined. The goal of these studies was to determine if sensitivity to cocaine reinforcement could be altered by acute presentation of environmental enrichment or stressors. Adult male dominant and subordinate cynomolgus monkeys self‐administered cocaine (0.003–0.1 mg/kg) under a concurrent schedule with 1‐g food pellets as the alternative; dose‐response curves were determined in single sessions. When SA was stable, one of two manipulations was performed prior to SA sessions: either the monkey was placed into a larger enclosure for 2 days or he was exposed to a toy snake for 10 min. Acute enrichment shifted the cocaine dose‐response curves to the right for all monkeys, while the acute stressor shifted the cocaine curves to the left only in subordinate monkeys. These results indicate that the model is sensitive to acute manipulations and that environmental enrichment impacts all monkeys, while the effects of stress are more prominent in subordinate monkeys. DA10584.

Effects of an acute social stressor on brain glucose utilization and cocaine self‐administration in socially housed monkeys

In monkeys, neurobiological differences related to social rafnk have been identified that are hypothesized to arise from chronic exposure to stress and have been shown to affect cocaine reinforcement. This study examined the effects of acute exposure to a social stressor on regional rates of cerebral glucose metabolism (CMRglc) and cocaine self‐administration in 4 dominant and 4 subordinate male cynomolgus monkeys. CMRglc was assessed using [18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET). Each monkey received FDG prior to placement in his home cage or a novel “intruder” cage which was surrounded by 4 unknown group‐housed monkeys for 40 min prior to a PET scan. At another time, exposure to each condition was followed by a self‐administration session in which cocaine (0.003–0.1 mg/kg) and food were concurrently available. In the FDG studies, CMRglc was reduced in motor, visual and somatosensory cortical areas and increased in anterior cingulate and basal ganglia in the intruder condition relative to control conditions; in addition, there were other changes related to social rank. Preliminary results show that acting as an intruder increased cocaine choice only in subordinate monkeys. These results document distinct patterns of neurobiological activity occurring after acute social stress that may enhance the reinforcing strength of cocaine in vulnerable individuals. DA10584, DA06634.

Trait and state variables associated with social rank and cocaine abuse in female cynomolgus monkeys

Social rank has been shown to affect susceptibility to many diseases including drug addiction. In the present studies we examined several behavioral and neurochemical markers as possible predictors of eventual social rank (i.e. trait variables) in 16 female cynomolgus monkeys and assessed whether these markers changed after social housing (i.e., state variables). Body weight, cortisol levels and locomotor activity did not predict social rank. In contrast, eventual subordinate monkeys were more impulsive as shown by lower latencies to approach a novel object in the home cage and had significantly higher levels of cerebrospinal fluid serotonin (5‐HT), but not dopamine (DA), metabolites (5‐HIAA and HVA, respectively). Using positron emission tomography, neither 5‐HT transporter nor DA D2 receptor availability was predictive of eventual social rank. However, as was observed in earlier studies with male monkeys, D2 receptor availability increased in monkeys that became dominant. Low D2 receptor availability and low social rank have been associated with heightened vulnerability to reinforcing effects of cocaine (Morgan et al. 2002; Nader et al. 2006); this association is currently being investigated. DA017763.

Sequence Variation in the Primate Dopamine Transporter Gene and Its Relationship to Social Dominance

Dopaminergic activity differs between socially dominant and subordinate monkeys, and in humans, it correlates significantly with extraversion, a trait analogous to social dominance in monkeys. Furthermore, concentrations of monoamine metabolites within the cerebrospinal fluid are highly heritable. Dopaminergic activity is modulated by the dopamine transporter (DAT), and the gene encoding this transporter is therefore an excellent candidate for studies aiming to identify variants of functional or evolutionary significance. However, the majority of such research has focused exclusively on the human homologue and its most common polymorphism, a functional variable number tandem repeat in the 3' untranslated region. Cross-species comparisons provide valuable insights into genome evolution, speciation, and selection mechanisms and may highlight sites of evolutionary significance. To date, however, no comprehensive studies of the DAT gene have been performed simultaneously on multiple primate species. We therefore characterized sequence variation and extent of linkage disequilibrium (LD) across the DAT genes of cynomolgus macaques (Macaca fascicularis), rhesus macaques (Macaca mulatta), and humans. We identified 2 potentially functional variants, which are associated with social rank in cynomolgus monkeys and which correspond to a putative transcription factor-binding site. Although highly conserved across mammals, the DAT gene differs significantly between humans and macaques in levels of sequence variation and LD structure, with the monkeys displaying up to 3 times more sequence variability and significantly less LD than humans. This suggests that the DAT gene has followed different evolutionary trajectories during primate speciation.

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1473-1482). Monkeys that have been trained to self administer an intravenous dose of cocaine by pressing a lever are more likely to administer the drug if they are lower in the social hierarchy. Moreover, although prolonged drug use reduces D2 receptor levels in both dominant and subordinate monkeys, D2 levels in dominant animals begin to rebound after several months of abstinence while those of subordinate monkeys do not. This growing body of evidence suggests that interventions that boost D2 dopamine receptors, whether drugs or other therapies, may help treat alcoholism or other addictions or may help protect individuals who have a genetic predisposition from developing these disorders. Drug interventions may be problematic because of the complexity of the dopamine system, said Gene-Jack Wang, MD, of the Brookhaven National Laboratory in Upton, NY, and a member of the research team. However, environmental interventions have shown promise. For instance, exercise has been shown to boost D2 dopamine receptor levels, Wang said. And, as Nader’s studies suggest, boosting an individual’s positive social interactions might be another approach. Perhaps the most important finding of the study is the hopeful message it sends individuals with a family history of alcoholism. “This study helps us understand the fundamental nature of the behavior of alcoholism,” Wang said. “Just because a person is born with a genetic predisposition to alcoholism doesn’t mean that’s it. There are things that can help them.”

Assessment of the relative reinforcing strength of cocaine in socially housed monkeys using a choice procedure.

Position in the social hierarchy can influence brain dopamine function and cocaine reinforcement in nonhuman primates during early cocaine exposure. With prolonged exposure, however, initial differences in rates of cocaine self-administration between dominant and subordinate monkeys dissipate. The present studies used a choice procedure to assess the relative reinforcing strength of cocaine in group-housed male cynomolgus monkeys with extensive cocaine self-administration histories. Responding was maintained under a concurrent fixed-ratio 50 schedule of food and cocaine (0.003-0.1 mg/kg per injection) presentation. Responding on the cocaine-associated lever increased as a function of cocaine dose in all monkeys. Although response distribution was similar across social rank when saline or relatively low or high cocaine doses were the alternative to food, planned t tests indicated that cocaine choice was significantly greater in subordinate monkeys when choice was between an intermediate dose (0.01 mg/kg) and food. When a between-session progressive-ratio procedure was used to increase response requirements for the preferred reinforcer (either cocaine or food), choice of that reinforcer decreased in all monkeys. The average response requirement that produced a shift in response allocation from the cocaine-associated lever to the food-associated lever was higher in subordinates across cocaine doses, an effect that trended toward significance (p = 0.053). These data indicate that despite an extensive history of cocaine self-administration, most subordinate monkeys were more sensitive to the relative reinforcing strength of cocaine than dominant monkeys.

Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration.

Disruption of the dopaminergic system has been implicated in the etiology of many pathological conditions, including drug addiction. Here we used positron emission tomography (PET) imaging to study brain dopaminergic function in individually housed and in socially housed cynomolgus macaques (n = 20). Whereas the monkeys did not differ during individual housing, social housing increased the amount or availability of dopamine D2 receptors in dominant monkeys and produced no change in subordinate monkeys. These neurobiological changes had an important behavioral influence as demonstrated by the finding that cocaine functioned as a reinforcer in subordinate but not dominant monkeys. These data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.