Establishment of Depression Behavioral Criteria in Cynomolgus Monkeys

Abstract

Depression is a common mental disorder with relatively high lifetime prevalence and substantial disability, especially in women [1][2][3]. Clinical manifestations of depression include loss of interest or pleasure, disturbed sleep or appetite, poor concentration, etc., worst of which is suicide. To solve such an important global public health issue, it is essential to establish ideal animal models for study and treatment of depression. Cynomolgus monkeys have been proved to be advantageous for modeling human depression through mother-infant separation [4] and social subordination stress [5].Behavioral tests have been performed in animals to test severity of depression and successfulness of modeling, for example, forced swim test and tail suspension test for rodents [6,7] and sucrose intake test for nonhuman primates [8]. In this study, we attempted to establish several behavioral criteria that can be easily measured to distinguish depression in cynomolgus monkeys.After a fourteen-month observation in groups, six socially subordinate female cynomolgus monkeys and six socially dominant counterparts were chosen as depressed models and alert controls, respectively, based on their social status hierarchy (Figure 1). The subordinate and dominant monkeys came from six and four groups, respectively, and each group consisted of 14-26 monkeys. The monkeys were 6-10 years of age and housed alone in adjacent cages separated with transparent plexiglass. All the monkeys were provided by Suzhou Xishan Zhongke Lab Animal Ltd (Suzhou, China) and received humane care.In this study, body weight, food consumption, preference for sucrose water, attempts for apple, and time of depressed posture were measured. Data are expressed as mean AE SEM and analyzed with unpaired t-test. P < 0.05 was considered statistically significant. The body weight of depressed monkeys was significantly lower than that of nondepressed monkeys (3.03 AE 0.07 vs. 3.57 AE 0.13 kg, P < 0.01; Figure 2A). Food consumption relative to body weight was calculated as the mean of 3-day measurements. Our results showed that depressed monkeys ate more food than the nondepressed (40.76 AE 2.76 vs. 18.25 AE 0.86 g/kg, P < 0.01; Figure 2B). The monkeys were deprived of water for 23 h and obliged to drink from two bottles containing pure water at the 24th h. After a 3-day adaptation, pure water was changed to 1.5% sucrose water in one bottle and then consumption of both kinds of water was recorded for 3 days. Preference of sucrose water was calculated as the percentage of sucrose water intake to total water intake. Depressed monkeys exhibited less preference for sucrose as compared to nondepressed monkeys (51.5 AE 12.6% vs. 81.0 AE 2.9%, P < 0.05; Figure 2C).Apples were given to monkeys in the cages for 3 days and then put out of the cages. Distance between the wall of the cage and the apple was a bit longer than the length of the monkey ' s arm. Monkeys could stretch their arms through the meshes of the cage wall. Times of reaching for apple were counted for 15 min on 3 day...

Chronic unpredictable mild stress produces depressive-like behavior, hypercortisolemia, and metabolic dysfunction in adolescent cynomolgus monkeys

“…Less sucrose consumption was observed in adult rhesus macaques following chronic glucocorticoid exposure 29 , a model of depressive-like behavior, while more was observed in adolescent monkeys that demonstrated depressive-like behaviors following social isolation 30 . Recently, Fan et al reported that the attempt for apple test (AAT) appeared to reliably measure anhedonia in cynomolgus monkeys 23 . In our study, SPT and AAT were both conducted to examine anhedonia, but only the AAT differentiated between the control and stressed groups.…”

“…We measured body weight and sucrose preference test (SPT) 22 at baseline and the end of each stress cycle. In addition, the attempt for apple test (AAT) 23 and human intruder test (HIT) 24 were conducted at the end of the five stress cycles. In the AAT, the fewer attempts for apples than controls was considered as anhedonia, which is a core symptom of patients with depression 23 .…”

“…In addition, the attempt for apple test (AAT) 23 and human intruder test (HIT) 24 were conducted at the end of the five stress cycles. In the AAT, the fewer attempts for apples than controls was considered as anhedonia, which is a core symptom of patients with depression 23 . In the HIT, the total time spent freezing, scratching, yawning, and showing a fear grimace were defined as anxious behaviors 24 .…”