, Volume 236, Issue 9, pp 2785–2796 | Cite as

Effects of early life stress on cocaine self-administration in post-pubertal male and female rhesus macaques

  • Alison G. P. WakefordEmail author
  • Elyse L. Morin
  • Sara N. Bramlett
  • Brittany R. Howell
  • Kai M. McCormack
  • Jerrold S. Meyer
  • Michael A. Nader
  • Mar M. Sanchez
  • Leonard L. Howell
Original Investigation



Early life stress (ELS), including childhood maltreatment, is a predictive factor for the emergence of cocaine use disorders (CUDs) in adolescence.


Accordingly, we examined whether post-pubertal male and female rhesus macaques that experienced infant maltreatment (maltreated, n = 7) showed greater vulnerability to cocaine self-administration in comparison with controls (controls, n = 7).


Infant emotional reactivity was measured to assess differences in behavioral distress between maltreated and control animals as a result of early life caregiving. Animals were then surgically implanted with indwelling intravenous catheters and trained to self-administer cocaine (0.001–0.3 mg/kg/infusion) under fixed-ratio schedules of reinforcement. Days to acquisition, and sensitivity to (measured by the EDMax dose of cocaine) and magnitude (measured by response rates) of the reinforcing effects of cocaine were examined in both groups.


Maltreated animals demonstrated significantly higher rates of distress (e.g., screams) in comparison with control animals. When given access to cocaine, control males required significantly more days to progress through terminal performance criteria compared with females and acquired cocaine self-administration slower than the other three experimental groups. The dose that resulted in peak response rates did not differ between groups or sex. Under 5-week, limited-access conditions, males from both groups had significantly higher rates of responding compared with females.


In control monkeys, these data support sex differences in cocaine self-administration, with females being more sensitive than males. These findings also suggest that ELS may confer enhanced sensitivity to the reinforcing effects of cocaine, especially in males.


Self-administration Early life stress Nonhuman primates Cocaine Sex differences 



The authors would like to thank Erin Siebert, Juliet Brown, Marisa Olsen, Jodi Manvich, Sarah Katznelson, Hannah Shields, Anne Glenn, Dora Guzman, Christine Marsteller, and Jennifer White for their invaluable technical assistance with these experiments.

Funding information

This research was supported by NIH grants DA038588 (MMS/LLH), DA010344 (LLH), DA031246 (LLH), MH078105 (MMS, project 3), and P51 OD11132 (Yerkes National Primate Research Center -YNPRC- base grant). The YNPRC is fully accredited by AAALAC International.

Compliance with ethical standards

Statement of conflict of interest

The authors declare that they have no conflicts of interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Alison G. P. Wakeford
    • 1
    • 2
    Email author
  • Elyse L. Morin
    • 1
    • 2
  • Sara N. Bramlett
    • 1
    • 2
  • Brittany R. Howell
    • 1
    • 2
    • 3
  • Kai M. McCormack
    • 1
    • 4
  • Jerrold S. Meyer
    • 5
  • Michael A. Nader
    • 6
  • Mar M. Sanchez
    • 1
    • 2
  • Leonard L. Howell
    • 2
    • 7
  1. 1.Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research CenterEmory UniversityAtlantaUSA
  2. 2.Department of Psychiatry & Behavioral SciencesEmory UniversityAtlantaUSA
  3. 3.Institute of Child DevelopmentUniversity of MinnesotaMinneapolisUSA
  4. 4.Department of PsychologySpelman CollegeAtlantaUSA
  5. 5.Department of Psychological & Brain SciencesUniversity of MassachusettsAmherstUSA
  6. 6.Department of Physiology and PharmacologyWake Forest School of MedicineWinston-SalemUSA
  7. 7.Division of Neuropharmacology and Neurologic Diseases, Yerkes National Primate Research CenterEmory UniversityAtlantaUSA

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