Analysis of Spontaneous Behavior Patterns of Male Rhesus Macaques Exposed to Voluntary Ethanol Consumption Over Two-Year Period

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Abstract

BACKGROUND: The onset of mental disorders associated with chronic ethanol use without dependence and safe threshold for alcohol consumption remain unclear.

AIM: To describe changes in the spontaneous behavior patterns of rhesus macaques in response to long-term alcohol consumption in a free-choice model.

MATERIAL AND METHODS: Behavioral responses of mature male rhesus macaques were evaluated using the ethogram-based time-interval method. The study included six animals with low ethanol consumption and eight animals with high ethanol consumption. Ethanol consumption was measured prior to (baseline) and during the initiation period (62 days) and at the start and end of the phase of alcohol motivation maintenance (688 days of continuous access to 4% ethanol and water). Two 30-day withdrawal periods were completed in the middle and end of the motivation maintenance phase. Analysis of variance was conducted using the Kruskal–Wallis test.

RESULTS: During the initiation phase and two motivation maintenance periods, the median ethanol consumption was 0.6, 0.5, and 0.8 g/kg/day for the low-consumption group and 1.6, 2.4, and 2.8 g/kg/day for the high-consumption group, respectively. The animals from the high-consumption group demonstrated a 9% decrease in body weight by the end of the observation period (p = 0.030). Ultrasound examination showed no hepatic or cardiac abnormalities. The baseline intergroup differences in stereotypy (p = 0.023), front-of-cage position (p = 0.023), and sitting position (p = 0.006) persisted throughout the experimental period. At the end of the motivation maintenance phase, the low-consumption group revealed a lower frequency of the slumped posture (p = 0.035). However, an increase was noted in the frequency of the front-of-cage position in the high-consumption group (76%; 60%–98% confidence interval; p = 0.006) compared to baseline (48%; 28%–63% confidence interval), which remained increased in the subsequent withdrawal period (83%; 53%–95% confidence interval; p = 0.008).

CONCLUSION: The 2-year alcohol consumption of male rhesus macaques in the free-choice model induced transient and prolonged changes in the spontaneous behavior patterns of the animals.

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About the authors

Roman M. Kirgintsev

Kurchatov medical primatology complex — National Research Centre «Kurchatov Institute»

Author for correspondence.
Email: feelmade.inc@gmail.com
ORCID iD: 0000-0003-4453-6811
SPIN-code: 8210-7467
ResearcherId: ACY-1999-2022

Postgraduate Student, Junior Research Associate, Lab. of Molecular Biology

Russian Federation, 177 Akademika Lapina st, Veseloe village, Adler district, Sochi, 354376

Laura E. Pavlova

Kurchatov medical primatology complex — National Research Centre «Kurchatov Institute»

Email: pavlova_laura@mail.ru
ORCID iD: 0000-0002-0638-0986
SPIN-code: 1437-4004

Research Associate, Lab. of Molecular Biology

Russian Federation, 177 Akademika Lapina st, Veseloe village, Adler district, Sochi, 354376

Maria F. Timina

Kurchatov medical primatology complex — National Research Centre «Kurchatov Institute»

Email: free_marshmallows@mail.ru
ORCID iD: 0000-0002-1916-238X
SPIN-code: 2506-1965

Postgraduate Student, Junior Research Associate, Lab. of Molecular Biology

Russian Federation, 177 Akademika Lapina st, Veseloe village, Adler district, Sochi, 354376

Andrey V. Panchenko

Kurchatov medical primatology complex — National Research Centre «Kurchatov Institute»

Email: ando_pan@mail.ru
ORCID iD: 0000-0002-5346-7646
SPIN-code: 4741-1855
ResearcherId: B-7345-2016

MD, Dr. Sci. (Medicine), Leading Research Associate, Scientific Lab. of Carcinogenesis and Aging

Russian Federation, 177 Akademika Lapina st, Veseloe village, Adler district, Sochi, 354376

Alla V. Panchenko

Kurchatov medical primatology complex — National Research Centre «Kurchatov Institute»

Email: shmaliy.a.v@gmail.com
ORCID iD: 0000-0003-1294-751X
SPIN-code: 6426-5271

MD, Cand. Sci. (Medicine), Assistant Professor, Head of Quality Assurance of NBICS-pt

Russian Federation, 177 Akademika Lapina st, Veseloe village, Adler district, Sochi, 354376

References

  1. Shin SK, Kaiser EE, West FD. Alcohol induced brain and liver damage: advantages of a porcine alcohol use disorder model. Front Physiol. 2021;11(592950):1–15. doi: 10.3389/fphys.2020.592950 EDN: MCXMBD
  2. Nikiforov AI, Rakitin MM, Merkin AG, et al. Neurologic complications of alcoholism. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(4):95–100. doi: 10.14412/2074-2711-2017-4-95-100 EDN: ZXXLEX
  3. Lee DI, Kim S, Kang DO. Exploring the complex interplay between alcohol consumption and cardiovascular health: Mechanisms, evidence, and future directions. Trends Cardiovasc Med. 2025:S1050–1738(25)00005–2. doi: 10.1016/j.tcm.2024.12.011
  4. Zahr NM, Pfefferbaum A. Alcohol’s effects on the brain: neuroimaging results in humans and animal models. Alcohol Res. 2017;38(2):183–206. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC5513685/
  5. Sari Y. Commentary: Targeting NMDA receptor and serotonin transporter for the treatment of comorbid alcohol dependence and depression. Alcohol Clin Exp Res. 2017;41(2):275–278. doi: 10.1111/acer.13310
  6. Polunina AG, Bryun EA. Macrostructural brain alterations in chronic alcohol abusers. Narcology. 2017;16(12(192)):63–71. EDN: ZWTFFN
  7. Sullivan EV, Pfefferbaum A. Brain-behavior relations and effects of aging and common comorbidities in alcohol use disorder: a review. Neuropsychology. 2019;33(6):760–780. doi: 10.1037/neu0000557
  8. Peshkovskaya AG, Galkin SA, Bokhan NA. Cognition in alcohol dependence: review of concepts, hypotheses and research methods. Siberian journal of psychology. 2023;87:138–158. doi: 10.17223/17267080/87/8 EDN: ATOVMG
  9. Galkin SA. Factors of reward-based decision-making in patients with alcohol dependence. Journal of addiction problems. 2022;11–12(213):67–76. EDN: ZGWBKY
  10. Iancu OD, Colville A, Walter NAR, et al. On the relationships in rhesus macaques between chronic ethanol consumption and the brain transcriptome. Addict Biol. 2018;23(1):196–205. doi: 10.1111/adb.12501
  11. Topiwala A, Ebmeier KP, Maullin-Sapey T, Nichols TE. Alcohol consumption and MRI markers of brain structure and function: cohort study of 25,378 UK Biobank participants. Neuroimage Clin. 2022;35:103066. doi: 10.1016/j.nicl.2022.103066 EDN: FSQYFO
  12. Mezue K, Osborne MT, Abohashem S, et al. Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk. J Am Coll Cardiol. 2023;81(24):2315–2325. doi: 10.1016/j.jacc.2023.04.015 EDN: JDLHPP
  13. Glantz MD. Addiction models and the challenge of having impact. Alcohol Clin Exp Res. 2019;43(9):1823–1828. doi: 10.1111/acer.14136
  14. Shnitko TA, Gonzales SW, Newman N, Grant KA. Behavioral flexibility in alcohol-drinking monkeys: the morning after. Alcohol Clin Exp Res. 2020;44(3):729–737. doi: 10.1111/acer.14289 EDN: VMCODC
  15. Kirgintsev RM, Pavlova LE, Timina MF, et al. Indicators of spontaneous behavior of rhesus monkeys with short-term course alcohol self-administration under free choice. S.S. Korsakov Journal of Neurology and Psychiatry. 2023;123(10):106–112. doi: 10.17116/jnevro2023123101106 EDN: JHXCST
  16. Panchenko AnV, Panchenko AlV, Pavlova LE, et al. Certain blood count and oxidative stress indicators during chronic alcohol consumption by rhesus monkeys in a free-choice model. Journal of addiction problems. 2023;35(2):37–51. doi: 10.47877/0234-0623_2021_06_41 EDN: QMBZTO
  17. Panchenko AlV, Kirgintsev RM, Pavlova LE, Panchenko AnV. The effect of chronic alcohol consumption on the cortisol, dehydroepiandrosterone sulphate and testosterone level in the blood of male rhesus monkeys. Journal of addiction problems. 2023;35(6):60–74. EDN: TKYDQU
  18. Camus SM, Blois-Heulin C, Li Q, et al. Behavioural profiles in captive-bred cynomolgus macaques: towards monkey models of mental disorders? PLoS One. 2013;8(4):e62141. doi: 10.1371/journal.pone.0062141
  19. Argo A, Pitingaro W, Puntarello M, et al. A comprehensive review on alcohol abuse disorder fatality, from alcohol binges to alcoholic cardiomyopathy. Diagnostics. 2024;14(11):1189. doi: 10.3390/diagnostics14111189 EDN: RJTULY
  20. Wang H, Tan T, Wang J, et al. Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis. Sci Rep. 2015;5(1):15019. doi: 10.1038/srep15019
  21. Lutz CK, Coleman K, Hopper LM, et al. Nonhuman primate abnormal behavior: etiology, assessment, and treatment. Am J Primatol. 2022;84(6):e23380. doi: 10.1002/ajp.23380 EDN: JSEWNY
  22. Kroenke CD, Rohlfing T, Park B, et al. Monkeys that voluntarily and chronically drink alcohol damage their brains: a longitudinal MRI study. Neuropsychopharmacology. 2014;39(4):823–830. doi: 10.1038/npp.2013.259
  23. Lundgaard I, Wang W, Eberhardt A, et al. Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function. Sci Rep. 2018;8(1):2246. doi: 10.1038/s41598-018-20424-y EDN: PXORSD
  24. Salinas AG, Mateo Y, Carlson VCC, et al. Long-term alcohol consumption alters dorsal striatal dopamine release and regulation by D2 dopamine receptors in rhesus macaques. Neuropsychopharmacology. 2021;46(8):1432–1441. doi: 10.1038/s41386-020-00938-8 EDN: LAXCYV
  25. Castillo-Carniglia A, Keyes KM, Hasin DS, Cerdá M. Psychiatric comorbidities in alcohol use disorder. Lancet Psychiatry. 2019;6(12):1068–1080. doi: 10.1016/S2215-0366(19)30222-6 EDN: SHODOI
  26. Ausderau KK, Colman RJ, Kabakov S, et al. Evaluating depression- and anxiety-like behaviors in non-human primates. Front Behav Neurosci. 2023;16:1006065. doi: 10.3389/fnbeh.2022.1006065
  27. Vetlugina TP, Nikitina VB, Lobacheva OA, et al. Cortisol and testosterone levels in alcoholic patients in withdrawal syndrome. Siberian Herald of Psychiatry and Addiction Psychiatry. 2017;3(96):5–10. doi: 10.26617/1810-3111-2017-3(96)-5-10
  28. Baker EJ, Moore S, Gonzales SW, Grant KA. Long-term drinking stability in the open-access self-administration monkey model. Alcohol. 2023;113:41–48. doi: 10.1016/j.alcohol.2023.07.002 EDN: RMZEUK

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Experimental design. The gray blocks represent behavior assessment sessions, whereas the white arrows refer to blood collection procedures. The solid black line is a visual marker, indicating the access to ethanol.

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3. Fig. 2. Common and atypical behavior patterns in rhesus macaques with a 2-year history of continuous alcohol consumption. a, Exploratory activity; b, motor activity; c, frequency of grooming behavior; and d, frequency of nail biting. *, p < 0.05; **, p < 0.01; ***, p < 0.001.

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4. Fig. 3. Displacement, aggressive, and stereotyped behavior patterns in rhesus macaques with a 2-year history of continuous alcohol consumption. a, Scratching; b, aggression; c, stereotypy; and d, stereotypic pacing. *, p < 0.05; **, p < 0.01; ***, p < 0.001.

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5. Fig. 4. Spatial positions in rhesus macaques with a 2-year history of continuous alcohol consumption. a, Front-of-cage position; b, upper-row position; c, facing the observer; d, four-legged posture; e, sitting position; and f, slumped posture. *, p < 0.05; **, p < 0.01; ***, p < 0.001.

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