Table 3.
Selected peer-reviewed publications describing methods of evaluation of depression- and anxiety-like behaviors in rhesus macaques (infant = 0–1 y; juvenile = 1–4 y; adult = 4–25 y).
| Reference | Age, Sex | Testing paradigm | Behavioral measures | Biological measures | Imaging |
|---|---|---|---|---|---|
| Rhesus Macaque (Macaca mulatta) | |||||
| Harlow and Suomi (1971) | Infants and juveniles, f & m | Social isolation | Self-clasp, huddle, locomotion, exploration | None | None |
| Suomi et al. (1975) | Adults, f & m | New groups of friends, friends, and strangers, or isolation | Self-groom, self-clasp, huddle, stereotypy | None | None |
| Amaral (2002) | Adults, m | Novel object, bilateral lesions to amygdala | Latency to take reward near novel object | None | None |
| Strome et al. (2002) | Juveniles, f & m | Isolation vs. social context, intraventricular CRF infusion | Huddle, face to wall, self-clasp, locomotion, exploration | Glucose metabolism in infundibulum, amygdala, and hippocampus | MRI, FDG-PET |
| Kalin and Shelton (2003) | Juveniles, f & m | Human intruder test, serotonin-transporter polymorphism, lesions to Ce, intraventricular CRF infusion | Freeze, coo vocalization | CSF and plasma cortisol μg/dl, glucose metabolism in infundibulum, amygdala, and hippocampus | MRI, FDG-PET |
| Erickson et al. (2005) | Infants, f & m | Maternal separation | Social behavior, grooming | Plasma cortisol, CSF metabolites serotonin, dopamine, NE | None |
| Kalin et al. (2005) | Juveniles, m | Human intruder test | Freeze | None | MRI, FDG-PET |
| Winslow (2005) | Infants, f & m | Maternal separation | Social deficits, vocalizations, stereotypy | Oxytocin, AVP | None |
| O’Connor and Cameron (2006) | Infants, f & m | Human intruder test, play test, maternal separation | Social contact, play, movement, vigilance, vocalizing, stereotypy | None | None |
| Kalin et al. (2007) | Juveniles, f & m | Human intruder test, predator test, lesion to orbitofrontal cortex | Locomotion, freeze, coo, bark, aggression to experimenter | EEG, plasma and CSF cortisol (μg/dl, Acth, crf (pg/ml) | None |
| Spinelli et al. (2012) | Infants, f & m | Chronic maternal separation | Self-directed behaviors, withdrawal, locomotion, vocalizations, exploration | None | None |
| Rogers et al. (2013) | Juveniles, f & m | Human intruder test | Locomotion, freeze, vocalizations | CRHR1 genotypes | MRI, FDG-PET |
| Qin et al. (2015) | Adults, f | Subordinate status in social group | Huddling, lack of responsiveness | Hair cortisol | SPECT-rCBF |
| Kalin et al. (2016) | Juveniles, f & m | Human intruder test, CRF infusion | Freezing, cooing | Plasma cortisol | MRI, FDG-PET, fMRI |
| Zhang et al. (2016) | Juveniles, m | Early rearing adversity and later chronic stress (single housing with either space restriction, intimidation, long illumination, or fasting) | Huddling, decreased locomotion, decreased sexual behavior, repetitive stereotypies | Hair cortisol | None |
| Fox et al. (2019) | Juveniles, m | Human intruder test, over-expression of NTF3 in Ce and basal nucleus | Locomotion, freeze, vocalizations | RNA seq | MRI, FDG-PET |
| Kenwood and Kalin (2021) | Infants, juveniles and adults, f & m | Human intruder test, predator test, social behavior, lesions to Ce-region | Vocalization, freezing | CSF, plasma, and cortisol | MRI, FDG-PET |
| Villard et al. (2021) | Juveniles, m | Behaviorally inhibited (defined by BioBehavioral Assessment program) vs. randomly assigned age-matched control monkeys | None after the initial assessment | Histological analyses (volume and neuron number of hippocampus and amygdala | None |
| Wood et al. (2021) | Infants- sub-adult, f & m | 6 month behavior during acute and chronic separation from mother, 4 years human intruder test, random assignment to adoptive or birth mother | Inactivity from social or environmental cues at infant separation test, intruder test aggression latency to approach, activity, exploration, social contact or withdrawal, stereotypy, and threat behaviors | Plasma ACTH | None |
Abbreviations: y, years; ACTH, adrenocorticotropic hormone; AVP, vasopressin; Ce, central nucleus of the amygdala; CRF, corticotropin-releasing factor; CRHR1, CRH receptor 1gene; CSF, cerebral spinal fluid; dl, deciliter; EEG, electroencephalography; f, female; FDG, 18F-fluorodeoxyglucose (for glucose activity); fMRI, functional magnetic resonance imaging; m, male; MRI, magnetic resonance imaging; NE, norepinephrine; NTF3, neurotrophin-3 gene; PET, positron emission tomography; pg, picograms; rCBF, regional blood flow; RNA seq, RNA next generation sequencing; SPECT, single photon emission computed tomography.