Social status, environment, and atherosclerosis in cynomolgus monkeys. Arteriosclerosis 2:359-368

Arteriosclerosis (Dallas, Tex.) 09/1982; 2(5):359-68. DOI: 10.1161/01.ATV.2.5.359
Source: PubMed

ABSTRACT The purpose of this experiment was to examine the effects of social environment and social status on coronary artery and aortic atherosclerosis in adult male cynomolgus monkeys (Macaca fascicularis). Thirty experimental animals were assigned to six groups of five members each, and all animals were fed a moderately atherogenic diet (43% of calories as fat, 0.34 mg cholesterol/Cal) for 22 months. Group memberships were changed periodically among 15 monkeys (unstable social condition) and remained fixed throughout the experiment in the remaining animals (stable social condition). Within each condition, individual monkeys were classified as either dominant or subordinate animals, based on dyadic patterns of aggression and submission. At necropsy, the coronary arteries were subjected to pressure fixation and five sections each were taken from the left anterior descending, left circumflex, and right coronary arteries. The mean intimal area measurement, based on all arterial sections, served as a coronary index for each animal. Results indicated that dominant animals in the unstable condition had significantly greater coronary artery atherosclerosis than dominant monkeys housed in stable social groups. Coronary artery atherosclerosis in the unstable dominants was also greater than among similarly housed (i.e., unstable) subordinates. A similar pattern was observed in the abdominal aorta, but was not statistically significant. No significant differences or similar patterns were seen in the thoracic aorta. Additional analyses revealed that the coronary artery effects were not due to concomitant differences in total serum cholesterol or high density lipoprotein cholesterol concentrations, blood pressures, ponderosity, or fasting glucose concentrations among the experimental animals. Behaviorally, manipulation of group memberships intensified agonistic encounters and disrupted patterns of affiliative interaction between dominant and subordinate monkeys. Overall, these results suggest that social dominance (an individual behavioral characteristic) is associated with increased coronary artery atherosclerosis, but only under social conditions that provide recurrent threats to the status of dominant animals (i.e., under behavioral challenge).

Download full-text


Available from: Jay R. Kaplan, Sep 29, 2015
55 Reads
  • Source
    • "Monkeys were separated daily for several hours during operant behavioral sessions and feeding. Social status had previously been determined for each monkey according to the outcomes of agonistic encounters using procedures similar to those described previously (see Kaplan et al., 1982; Czoty et al., 2005, 2009). Briefly, two observers separately conducted several 15-minute observation sessions per pen. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Dopamine D2/D3 receptor partial agonists have been suggested as medications for cocaine dependence. These experiments examined the effect of acute and repeated administration of drugs with varying intrinsic efficacy at D2/D3 receptors on the relative reinforcing strength of cocaine. Use of socially housed cynomolgus monkeys permitted the assessment of the whether social status, known to influence D2/D3 receptor availability, influenced the behavioral effects of D2/D3 receptor compounds. The high-efficacy agonist R(-)-norpropylapomorphine ((-)-NPA), low-efficacy agonist aripiprazole (ARI) and antagonist eticlopride (ETIC) were administered acutely to monkeys self-administering cocaine under a food-cocaine choice procedure in which a cocaine self-administration dose-effect curve was determined daily. The effects of 5-day treatment with ARI and (-)-NPA were characterized under conditions in which monkeys did (ARI) or did not (ARI and (-)-NPA) self-administer cocaine during treatment. When administered acutely, ARI and ETIC increased choice of low cocaine doses and only (-)-NPA decreased choice of higher cocaine doses and cocaine intake; effects were similar across social ranks. When administered repeatedly while self-administration occurred only on days 1 and 5 of treatment, ARI, but not (-)-NPA, decreased cocaine choice in dominant monkeys, whereas (-)-NPA but not ARI did so in subordinates. When dominant monkeys self-administered cocaine all five days of ARI treatment, however, these effects were not observed. The results indicate that the behavioral effects of D2/D3 receptor agonists can differ according to intrinsic efficacy and subject characteristics. Moreover, these results suggest that exposure to cocaine during treatment can counteract treatment-induced reductions in the reinforcing effects of cocaine.
    Journal of Pharmacology and Experimental Therapeutics 12/2012; 344(2). DOI:10.1124/jpet.112.201012 · 3.97 Impact Factor
  • Source
    • "In landmark studies, Kaplan and coworkers showed that atherosclerosis development was accelerated in dominant male cynomolgus monkeys living in unstable hierarchies [5] [6]. The effect on atherosclerosis was inhibited by nonselective í µí»½-blockade using propranolol [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE(-/-) mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE(-/-) mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P < 0.05 versus Control). Further, metoprolol reduced serum TNFα and the chemokine CXCL1 (P < 0.01 versus Control for both) as well as decreasing the macrophage content in the plaques (P < 0.01 versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE(-/-) mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFα and CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.
    06/2011; 12(1):71-71. DOI:10.1016/S1567-5688(11)70329-4
  • Source
    • "Studies Used in Meta-Analysis #Dominant #Subordinate Reference Studies with Males in Stable Groups MS1a 8 6 Kaplan et al. 1982 MS4a 11 4 Williams et al. 2003 MS5a 11 14 Williams et al. 1993 MS6 8 8 Hamm et al. 1983 MS7 13 17 Adams et al. 2005 Studies with Males in Reorganized Groups 1 MS1b 2 6 9 Kaplan et al. 1982 MS2a 2 6 6 Kaplan et al. 1987 MS2b 16 13 Kaplan et al. 1987 MS4b 10 8 Williams et al. 2003 MS5b 23 22 Williams et al. 1993 Studies of Females FS1 3 14 9 Kaplan et al. 1984 FS2a 41 46 Kaplan et al. 2002 FS2b 39 60 Kaplan et al. 1995 FS3 9 10 Adams et al. 2000 FS4 8 8 Hamm et al. 1983 FS5 21 22 Walker et al. 2008 1 "
    [Show abstract] [Hide abstract]
    ABSTRACT: More than 25 years ago our laboratory reported sex-dependent relationships between social status and coronary artery atherosclerosis among cholesterol-fed cynomolgus monkeys (Macaca fascicularis) maintained in social groups of four to six animals each. Dominant males developed more atherosclerosis than subordinates, but only if housed in recurrently reorganized social groups. In contrast, dominant females developed significantly less atherosclerosis than subordinates, irrespective of social setting. Although we have continued to study these associations, no confirmatory investigations have been reported by other laboratories or using other atherosclerosis-susceptible monkey species. Accordingly, we conducted a meta-analysis of all relevant data sources developed in our laboratory since 1982 to determine whether the originally reported relationships between social status and atherosclerosis reflected robust associations. The sentinel (first) studies were composed of 16 females and 27 males. The current meta-analysis encompassed 419 animals (200 females and 219 males) derived from 11 separate investigations. The results confirmed that, among males, dominant individuals developed more extensive atherosclerosis than subordinates when housed in recurrently reorganized (unstable) social groups in which an estrogen-implanted female was also present. Dominant males in stable social groups tended to have less atherosclerosis than similarly housed subordinates, but this effect was not significant. On the contrary, we found that dominant females developed reliably less atherosclerosis than subordinates.
    American Journal of Primatology 09/2009; 71(9):732-41. DOI:10.1002/ajp.20707 · 2.44 Impact Factor
Show more