Assessment of stress responses in rhesus macaques (Macaca mulatta) to daily routine procedures in system neuroscience based on salivary cortisol concentrations

PLoS One. 2018 Jan 2;13(1):e0190190. doi: 10.1371/journal.pone.0190190. eCollection 2018.


Non-human primates participating in neurophysiological research are exposed to potentially stressful experimental procedures, such as dietary control protocols, surgical implants and their maintenance, or social separation during training and experimental session. Here, we investigated the effect of controlled access to fluid, surgical implants, implant-related cleaning of skin margins, and behavioral training sessions on salivary cortisol levels of adult male rhesus macaques participating in neurophysiological research. The animals were trained to chew flavored cotton swabs to non-invasively collect saliva samples. Our data show no differences in cortisol levels between animals with and without implants, but both, controlled access to fluid and cleaning of implants individually increased salivary cortisol concentrations, while both together did not further increase the concentration. Specifically, before cleaning, individuals with controlled access to fluid had 55% higher cortisol concentrations than individuals with free access to fluid. Under free access to fluid, cortisol concentrations were 27% higher after cleaning while no effect of cleaning was found for individuals under controlled fluid access. Training sessions under controlled access to fluid also did not affect salivary cortisol concentrations. The observed changes in cortisol concentrations represent mild stress responses, as they are only a fraction of the range of the regular circadian changes in cortisol levels in rhesus monkeys. They also indicate that combinations of procedures do not necessarily lead to cumulative stress responses. Our results indicate that salivary cortisol levels of rhesus monkeys respond to neurophysiological experimental procedures and, hence, may be used to assess further refinements of such experimental methods.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hydrocortisone / analysis*
  • Macaca mulatta
  • Male
  • Saliva / chemistry*
  • Stress, Physiological*


  • Hydrocortisone

Grants and funding

The study was supported by the European Commission in the context of the EUPRIM-Net-II consortium FP7-262443-WP9 (; assigned to ST & AG) and the German Research Foundation ( Research Units 1847 (ST, AG) and 2591 (ST, AG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.