Psychopharmacology

, Volume 224, Issue 1, pp 133–143 | Cite as

Social rank, chronic ethanol self-administration, and diurnal pituitary–adrenal activity in cynomolgus monkeys

  • Christa M. Helms
  • Megan N. McClintick
  • Kathleen A. Grant
Original Investigation

Abstract

Rationale

Dominance hierarchies affect ethanol self-administration, with greater intake among subordinate animals compared to dominant animals. Excessive ethanol intake disrupts circadian rhythms. Diurnal rhythms of the hypothalamic–pituitary–adrenal axis have not been characterized in the context of ethanol self-administration with regard to social rank.

Objective

This study aimed to determine whether diurnal pituitary–adrenal hormonal rhythms account for differences between social ranks in ethanol self-administration or are differentially affected by ethanol self-administration between social ranks.

Methods

During alternating individual (n = 11–12) and social (n = 3 groups) housing of male cynomolgus monkeys (Macaca fascicularis), diurnal measures of cortisol and adrenocorticotropic hormone (ACTH) were obtained from plasma samples three times per week. Social rank was determined, ethanol (4 %, w/v) self-administration was induced, and then the monkeys were allowed a choice of water or ethanol for 22 h/day for 49 weeks.

Results

For all social ranks, plasma ACTH was elevated during social housing, but cortisol was stable, although greater among dominant monkeys. Ethanol self-administration blunted the effect of social housing, cortisol, and the diurnal rhythm for both hormones, regardless of daily ethanol intake (1.2–4.2 g/kg/day). Peak ACTH and cortisol were more likely to be observed in the morning during ethanol access. Ethanol, not vehicle, intake was lower during social housing across social ranks. Only dominant monkeys showed significantly lower blood–ethanol concentration during social housing.

Conclusions

There was a low threshold for disruption of diurnal pituitary rhythms by ethanol drinking, but sustained adrenal corticosteroid rhythms. Protection against heavy drinking among dominant monkeys may have constrained ethanol intoxication, possibly to preserve dominance rank.

Keywords

Ethanol HPA axis Stress Monkey Cortisol ACTH 

Notes

Acknowledgments

This work and preparation of the manuscript was supported by RR000163, AA019431, AA019355, AA10760, AA13541, AA13510, and T32AA007468.

Supplementary material

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Supplemental Fig. 1

Plasma ACTH and cortisol across the experiment among individual monkeys housed together in rack 1 (JPEG 85.0 kb)

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High resolution image (TIFF 644 kb)
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Supplemental Fig. 2

Plasma ACTH and cortisol across the experiment among individual monkeys housed together in rack 2 (JPEG 111 kb)

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High resolution image (TIFF 756 kb)
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Supplemental Fig. 3

Plasma ACTH and cortisol across the experiment among individual monkeys housed together in rack 3 (JPEG 68 kb)

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High resolution image (TIFF 486 kb)
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Supplemental Fig. 4

Mean weekly ethanol (closed) and vehicle (open) intake across the experiment among individual monkeys housed together in rack 1 (JPEG 36 kb)

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High resolution image (TIFF 213 kb)
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Supplemental Fig. 5

Mean weekly ethanol (closed) and vehicle (open) intake across the experiment among individual monkeys housed together in rack 2 (JPEG 85 kb)

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High resolution image (TIFF 515 kb)
213_2012_2707_Fig10_ESM.jpg (79 kb)
Supplemental Fig. 6

Mean weekly ethanol (closed) and vehicle (open) intake across the experiment among individual monkeys housed together in rack 3 (JPEG 78 kb)

213_2012_2707_MOESM6_ESM.tif (513 kb)
High resolution image (TIFF 512 kb)

References

  1. Abbott DH, Keverne EB, Bercovitch FB, Shively CA, Mendoza SP, Saltzman W, Snowdon CT, Ziegler TE, Banjevic M, Garland T Jr, Sapolsky RM (2003) Are subordinates always stressed? A comparative analysis of rank differences in cortisol levels among primates. Horm Behav 43:67–82PubMedCrossRefGoogle Scholar
  2. Balkin TJ, Braun AR, Wesensten NJ, Jeffries K, Varga M, Baldwin P, Belenky G, Herscovitch P (2002) The process of awakening: a PET study of regional brain activity patterns mediating the re-establishment of alertness and consciousness. Brain 125:2308–2319PubMedCrossRefGoogle Scholar
  3. Barr CS, Dvoskin RL, Yuan Q, Lipsky RH, Gupte M, Hu X, Zhou Z, Schwandt ML, Lindell SG, McKee M, Becker ML, Kling MA, Gold PW, Higley JD, Heilig M, Suomi SJ, Goldman D (2008) CRH haplotype predicts CSF CRH, HPA axis activity, temperament, and alcohol consumption in rhesus macaques. Arch Gen Psychiatry 65:934–944PubMedCrossRefGoogle Scholar
  4. Barr CS, Dvoskin RL, Gupte M, Sommer W, Sun H, Schwandt ML, Lindell SG, Kasckow JW, Suomi SJ, Goldman D, Higley JD, Heilig M (2009) Functional CRH variation increases stress-induced alcohol consumption in primates. PNAS 106:14593–14598PubMedCrossRefGoogle Scholar
  5. Blomeyer D, Treutlein J, Esser G, Schmidt MH, Schumann G, Laucht M (2008) Interaction between CRHR1 gene and stressful life events predicts adolescent heavy alcohol use. Biol Psychiatry 63:146–151PubMedCrossRefGoogle Scholar
  6. Bohem C (2004) Hierarchy in the forest: the evolution of egalitarian behavior. Harvard University Press, CambridgeGoogle Scholar
  7. Boschloo L, Vogelzangs N, Licht CMM, Vreeburg SA, Smit JH, van den Brink W, Veltman DJ, de Geus EJC, Beekman ATF, Penninx BWJH (2011) Heavy alcohol use, rather than alcohol dependence, is associated with dysregulation of the hypothalamic–pituitary–adrenal axis and the autonomic nervous system. Drug Alcohol Depend 116:170–176PubMedCrossRefGoogle Scholar
  8. Boyd KN, Kumar S, O’Buckley TK, Morrow AL (2010) Chronic ethanol exposure produces tolerance to elevations in neuroactive steroids: mechanisms and reversal by exogenous ACTH. J Neurochem 115:142–152PubMedCrossRefGoogle Scholar
  9. Chen CP, Kuhn P, Advis JP, Sarkar DK (2004) Chronic ethanol consumption impairs the circadian rhythm of pro-opiomelanocortin and period genes mRNA expression in the hypothalamus of the male rat. J Neurochem 88:1547–1554PubMedCrossRefGoogle Scholar
  10. Crowley TJ (1983) Substance abuse research in monkey social groups. Prog Clin Biol Res 131:255–275PubMedGoogle Scholar
  11. Cuzon Carlson VC, Seabold GK, Helms CM, Garg N, Odagiri M, Rau AR, Daunais J, Alvarez VA, Lovinger DM, Grant KA (2011) Synaptic and morphological neuroadaptations in the putamen associated with long-term, relapsing alcohol drinking in primates. Neuropsychopharmacology 36:2513–2528PubMedCrossRefGoogle Scholar
  12. Czoty PW, Morgan D, Shannon EE, Gage HD, Nader MA (2004) Characterization of dopamine D1 and D2 receptor function in socially housed cynomolgus monkeys self-administering cocaine. Psychopharmacology 174:381–388PubMedCrossRefGoogle Scholar
  13. Czoty PW, Gould RW, Nader MA (2008) Relationship between social rank and cortisol and testosterone concentrations in male cynomolgus monkeys (Macaca fascicularis). J Neuroendocrinol 21:68–76CrossRefGoogle Scholar
  14. Dong L, Bilbao A, Laucht M, Henriksson R, Yakovleva T, Ridinger M, Desrivieres S, Clarke T-K, Lourdusamy A, Smolka MN, Cichon S, Blomeyer D, Treutlein J, Perreau-Lenz S, Witt S, Leonardi-Essmann F, Wodarz N, Zill P, Soyka M, Albrecht U, Rietschel M, Lathrop M, Bakalkin G, Spanagel R, Schumann G (2011) Effects of the circadian rhythm gene period 1 (Per1) on psychosocial stress-induced alcohol drinking. Am J Psychiatry 168:1090–1098PubMedCrossRefGoogle Scholar
  15. Edwards S, Evans P, Hucklebridge F, Clow A (2001) Association between time of awakening and diurnal cortisol secretory activity. Psychoneuroendocrinology 26:613–622PubMedCrossRefGoogle Scholar
  16. Ehlers CJ, Walker BM, Pian JP, Roth JL, Slawecki CJ (2007) Increased alcohol drinking in isolate-housed alcohol-preferring rats. Behav Neurosci 121:111–119PubMedCrossRefGoogle Scholar
  17. Ekman A-C, Vakkuri O, Vuolteenaho O, Leppäluoto J (1994) Delayed pro-opiomelanocortin activation after ethanol intake in man. Alcohol Clin Exp Res 18:1226–1229PubMedCrossRefGoogle Scholar
  18. Flack JC, De Waal FBM (2004) Dominance style, social power, and conflict management: a conceptual framework. In: Thierry B, Singh M, Kaumanns W (eds) Macaque societies: a model for the study of social organization. Cambridge University Press, CambridgeGoogle Scholar
  19. Foley R, Gamble C (2009) The ecology of social transitions in human evolution. Phil Trans R Soc B 364:3267–3279PubMedCrossRefGoogle Scholar
  20. Fonzi S, Solinas GP, Costelli P, Parodi C, Murialdo G, Bo P, Albergati A, Montalbetti L, Savoldi F, Polleri A (1994) Melatonin and cortisol circadian secretion during ethanol withdrawal in chronic alcoholics. Chronobiologia 21:109–112PubMedGoogle Scholar
  21. Gonzalez CA, Gunnar MR, Levine S (1981) Behavioral and hormonal responses to social disruption and infant stimuli in female rhesus monkeys. Psychoneuroendocrinology 6:53–64PubMedCrossRefGoogle Scholar
  22. Goo GP, Sassenrath EN (1980) Persistent adrenocortical activation in female rhesus monkeys after new breeding group formation. J Med Primatol 9:325–334PubMedGoogle Scholar
  23. Grant KA, Shively CA, Nader MA, Ehrenkaufer RL, Line SW, Morton TE, Gage HD, Mach RH (1998) Effect of social status on striatal dopamine D2 receptor binding characteristics in cynomolgus monkeys assessed with positron emission tomography. Synapse 29:80–83PubMedCrossRefGoogle Scholar
  24. Grant KA, Leng X, Green HL, Szeliga KT, Rogers LS, Gonzales SW (2008) Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration. Alcohol Clin Exp Res 32:1824–1838PubMedCrossRefGoogle Scholar
  25. Herod SM, Dettmer AM, Novak MA, Meyer JS, Cameron JL (2011) Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis. Am J Physiol Endocrinol Metab 300:E28–E36PubMedCrossRefGoogle Scholar
  26. Higley JD, Hasert MF, Suomi SJ, Linnoila M (1991) Nonhuman primate model of alcohol abuse: effects of early experience, personality, and stress on alcohol consumption in nonhuman primates. Alcohol 34:402–418Google Scholar
  27. Higley JD, Suomi SJ, Linnoila M (1996) A nonhuman primate model of type II excessive alcohol consumption? Part 1. Low cerebrospinal fluid 5-hydroxyindoleaceetic acid concentrations and diminished social competence correlate with excessive alcohol consumption. Alcohol Clin Exp Res 20:629–642Google Scholar
  28. Huang M-C, Ho C-W, Chen C-H, Liu S-C, Chen C-C, Leu S-J (2010) Reduced expression of circadian clock genes in male alcoholic patients. Alcohol Clin Exp Res 34:1899–1904PubMedCrossRefGoogle Scholar
  29. Iranmanesh A, Veldhuis JD, Johnson ML, Lizarralde G (1989) 24-hour pulsatile and circadian patterns of cortisol secretion in alcoholic men. J Androl 10:54–63PubMedGoogle Scholar
  30. Kakihana R, Moore JA (1976) Circadian rhythm of corticosterone in mice: the effect of chronic consumption of alcohol. Psychopharmacologia 46:301–305PubMedCrossRefGoogle Scholar
  31. Kraemer GW, McKinney WT (1985) Social separation increases alcohol consumption in rhesus monkeys. Psychopharmacology 104:367–376Google Scholar
  32. Krieger DT (1974) Food and water restriction shifts corticosterone, temperature, activity and brain amine periodicity. Endocrinology 95:1195–1201PubMedCrossRefGoogle Scholar
  33. Krieger DT, Hauser H, Krey LC (1977) Suprachiasmatic nuclear lesions do not abolish food-shifted circadian adrenal and temperature rhythmicity. Science 197:398–399PubMedCrossRefGoogle Scholar
  34. Lee S, Selvage D, Hansen K, Rivier C (2004) Site of action of acute alcohol administration in stimulating the rat hypothalamic–pituitary–adrenal axis: comparison between the effect of systemic and intracerebroventricular injection of this drug on pituitary and hypothalamic responses. Endocrinology 145:4470–4479PubMedCrossRefGoogle Scholar
  35. Lyons DM, Wang OJ, Lindley SE, Levine S, Kalin NH, Schatzberg AF (1999) Separation induced changes in squirrel monkey hypothalamic–pituitary–adrenal physiology resemble aspects of hypercortisolism in humans. Psychoneuroendocrinology 24:131–142PubMedCrossRefGoogle Scholar
  36. Matthews K, Schwartz J, Cohen S, Seeman T (2006) Diurnal cortisol decline is related to coronary calcification: CARDIA study. Psychosom Med 68:657–661PubMedCrossRefGoogle Scholar
  37. McKenzie-Quirk SD, Miczek KA (2008) Social rank and social separation as determinants of alcohol drinking in squirrel monkeys. Psychopharmacology 201:137–145PubMedCrossRefGoogle Scholar
  38. Meier AH (1976) Daily variation in concentration of plasma corticosteroid in hypophysectomized rats. Endocrinology 98:1475–1479PubMedCrossRefGoogle Scholar
  39. Mendoza SP, Coe CL, Lowe EL, Levine S (1979) The physiological response to group formation in adult male squirrel monkeys. Psychoneuroendocrinology 3:221–229CrossRefGoogle Scholar
  40. Morgan D, Grant KA, Prioleau OA, Nader SH, Kaplan JR, Nader MA (2000) Predictors of social status in cynomolgus monkeys (Macaca fasicularis) after group formation. Am J Primatol 52:115–131PubMedCrossRefGoogle Scholar
  41. Morgan D, Grant KA, Gage HD, Mach RH, Kaplan JR, Prioleau O, Nader SH, Buchheimer N, Ehrenkaufer RL, Nader MA (2002) Social dominance in monkeys: dopamine D2 receptors and cocaine self-administration. Nat Neurosci 5:169–174PubMedCrossRefGoogle Scholar
  42. Mukherjee S, Kazerooni M, Simasko SM (2008) Dose–response study of chronic alcohol induced changes in sleep patterns in rats. Brain Res 1208:120–127PubMedCrossRefGoogle Scholar
  43. Oster H, Damerow S, Kiessling S, Jakubcakova V, Abraham D, Tian J, Hoffman MW, Eichele G (2006) The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. Cell Metab 4:163–173PubMedCrossRefGoogle Scholar
  44. Parker LF, Radow BL (1974) Isolation stress and volitional ethanol consumption in the rat. Physiol Behav 12:1–3PubMedCrossRefGoogle Scholar
  45. Porcu P, Sogliano C, Ibba C, Piredda M, Tocco S, Marra C, Purdy RH, Biggio G, Concas A (2004) Failure of γ-hydroxybutyric acid both to increase neuroactive steroid concentrations in adrenalectomized–orchiectomized rats and to induce tolerance to its steroidogenic effect in intact animals. Brain Res 1012:160–168PubMedCrossRefGoogle Scholar
  46. Porcu P, Rogers LS, Morrow AL, Grant KA (2006) Plasma pregnenolone levels in cynomolgus monkeys following pharmacological challenges of the hypothalamic–pituitary–adrenal axis. Pharmacol Biochem Behav 84:618–627PubMedCrossRefGoogle Scholar
  47. Richman JA, Shinsako SA, Rospenda KM, Flaherty JA, Freels S (2002) Workplace harassment/abuse and alcohol-related outcomes: the mediating role of psychological distress. J Stud Alcohol 63:412–419PubMedGoogle Scholar
  48. Riddick NV, Czoty PW, Gage HD, Kaplan JR, Nader SH, Icenhower M, Pierre PJ, Bennett A, Garg PK, Garg S, Nader MA (2009) Behavioral and neurobiological characteristics influencing social hierarchy formation in female cynomolgus monkeys. Neuroscience 158:1257–1265PubMedCrossRefGoogle Scholar
  49. Risher-Flowers D, Adinoff B, Ravitz B, Bone GH, Martin PR, Nutt D, Linnoila M (1988) Circadian rhythms of cortisol during alcohol withdrawal. Adv Alcohol Subst Abus 7:37–41CrossRefGoogle Scholar
  50. Rosenwasser AM, Logan RW, Fecteau ME (2005) Chronic ethanol intake alters circadian period-responses to brief light pulses in rats. Chronobiol Int 22:227–236PubMedCrossRefGoogle Scholar
  51. Rosmond R, Bjorntorp P (2000) The hypothalamic–pituitary–adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. J Intern Med 247:188–197PubMedCrossRefGoogle Scholar
  52. Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D (2000) Diurnal cortisol rhythm as a predictor of breast cancer survival. J Nat Cancer Inst 92:994–1000PubMedCrossRefGoogle Scholar
  53. Shively CA (1998) Social subordination stress, behavior, and central monoaminergic function in female cynomolgus monkeys. Biol Psych 44:882–891CrossRefGoogle Scholar
  54. Sillaber I, Rammes G, Zimmermann S, Mahal B, Zieglgänsberger W, Wurst W, Holsboer F, Spanagel R (2002) Enhanced and delayed stress-induced alcohol drinking in mice lacking function CRH1 receptors. Science 296:931–933PubMedCrossRefGoogle Scholar
  55. Spanagel R, Rosenwasser AM, Schumann G, Sarkar DK (2005) Alcohol consumption and the body’s biological clock. Alcohol Clin Exp Res 29:1550–1557PubMedCrossRefGoogle Scholar
  56. Thierry B (2007) Unity in diversity: lessons from macaque societies. Evol Anthropol 16:224–238CrossRefGoogle Scholar
  57. Torres-Farfan C, Valenzuela FJ, Ebensperger R, Méndez N, Campino C, Richter HG, Valenzuela GJ, Serón-Ferré M (2008) Circadian cortisol secretion and circadian adrenal responses to ACTH are maintained in dexamethasone suppressed capuchin monkeys (Cebus paella). Am J Primtol 70:93–100CrossRefGoogle Scholar
  58. Urbanski HF (2011) Role of circadian neuroendocrine rhythms in the control of behavior and physiology. Neuroendocrinology 93:211–222PubMedCrossRefGoogle Scholar
  59. Vivian JA, Green HL, Young JE, Majerksy LS, Thomas BW, Shively CA, Tobin JR, Nader MA, Grant KA (2001) Induction and maintenance of ethanol self-administration in cynomolgus monkeys (Macaca fascicularis): long-term characterization of sex and individual differences. Alcohol Clin Exp Res 25:1087–1097PubMedCrossRefGoogle Scholar
  60. Welker C, Schäfer-Witt C, Voigt K (1992) Social position and personality in Macaca fascicularis. Folia Primatol 58:112–117CrossRefGoogle Scholar
  61. Wilhelm I, Born J, Kudielka BM, Schlotz W, Wüst S (2007) Is the cortisol awakening rise a response to awakening? Psychoneuroendocrinology 32:358–366Google Scholar
  62. Wilson ME, Legendre A, Pazol K, Fisher J, Chikazawa K (2005) Gonadal steroid modulation of the limbic–hypothalamic–pituitary–adrenal (LHPA) axis is influenced by social status in female rhesus monkeys. Endocrine 26:89–97PubMedCrossRefGoogle Scholar
  63. Winslow JT, Miczek KA (1985) Social status as a determinant of alcohol effects on aggressive behavior in squirrel monkeys (Saimiri sciureus). Psychopharmacology 85:167–172PubMedCrossRefGoogle Scholar
  64. Wolf OT (2009) Stress and memory in humans: twelve years of progress? Brain Res 1293:142–154PubMedCrossRefGoogle Scholar
  65. Wolffgramm J, Heyne A (1991) Social behavior, dominance, and social deprivation of rats determine drug choice. Pharmacol Biochem Behav 38:389–399PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Christa M. Helms
    • 1
  • Megan N. McClintick
    • 1
  • Kathleen A. Grant
    • 1
    • 2
  1. 1.Oregon National Primate Research CenterOregon Health and Science UniversityBeavertonUSA
  2. 2.Department of Behavioral NeuroscienceOregon Health and Science UniversityPortlandUSA

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