Behavioral depression and positron emission tomography-determined serotonin 1A receptor binding potential in cynomolgus monkeys.
BACKGROUND
Current animal models of depression are inadequate to further our understanding of depression. New models that allow for analysis of cognitive function and sex differences are needed.


OBJECTIVE
To characterize serotonin 1A (5-HT(1A)) receptor binding potential (BP) and its relationship with specific characteristics of behavioral depression in cynomolgus monkeys.


METHODS
A 23-month case-control study.


METHODS
Small social groups in the laboratory. Subjects Seventeen adult female cynomolgus monkeys.


METHODS
Serotonin 1A receptor BP was examined by positron emission tomography using the radioligand 4,2"-(methoxyphenyl)-1-[2"-(N-2"-pyridinyl)-p-fluorobenzamido]ethylpiperazine in the raphe, amygdala, hippocampus, and anterior cingulate cortex in monkeys characterized by behavioral observation as depressed or not depressed. Aggression, submission, affiliation, pathologic behaviors, and activity levels were determined by behavioral observation. Heart rate and hypothalamic-pituitary-adrenal function were also determined.


RESULTS
Throughout the brain areas examined, there was a reduction in 5-HT(1A) BP in depressed monkeys. The 5-HT(1A) BP in the amygdala and hippocampus was associated with aggression and submission. Friendly interaction, grooming, and locomotion were associated with 5-HT(1A) BP in the left cingulate cortex, whereas attention directed toward the environment was associated with 5-HT(1A) BP in the right cingulate cortex. The 5-HT(1A) receptor BP was inversely associated with heart rate in the raphe, left cingulate, and right amygdala.


CONCLUSIONS
This is the fourth in a series of studies that suggest that depressive behavior in adult female cynomolgus monkeys is similar to that observed in humans. It has been observed in 2 large groups of monkeys randomly selected from feral populations, suggesting that the capacity for depression is inherent in the species. This animal model holds promise to further our understanding of the basic mechanisms of affective behavior, the neuropathophysiologic characteristics of depression and the cognitive dysfunction that accompanies them, genetic and environmental factors that may affect depression risk, and the role of reproductive function in the excess depression risk in women.
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. cshively@wfubmc.edu
Carol A
CA
Shively
David P
DP
Friedman
H Donald
HD
Gage
Michael C
MC
Bounds
Clive
C
Brown-Proctor
Joseph B
JB
Blair
Jessica A
JA
Henderson
Michael A
MA
Smith
Nancy
N
Buchheimer
D000374:Aggression / Q000502:physiology / Q000523:psychology; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D003907:Dexamethasone; D004195:Disease Models, Animal; D005260:Female; D019788:Fluorodeoxyglucose F18; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008252:Macaca fascicularis / Q000378:metabolism*; D010879:Piperazines; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data*; D011725:Pyridines; D011869:Radioligand Assay; D019275:Radiopharmaceuticals; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
D002352:Carrier Proteins; D010879:Piperazines; D011725:Pyridines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D044282:Receptor, Serotonin, 5-HT1A; D003907:Dexamethasone; D006854:Hydrocortisone