Neonatal amygdala lesions alter basal cortisol levels in infant rhesus monkeys

Abstract

The amygdala is mostly thought to exert an excitatory influence on the hypothalamic-pituitary-adrenal (HPA) axis, although its role regulating HPA basal tone is less clear, particularly during primate development. The current study examined the effects of neonatal amygdala lesions on basal HPA function and the postnatal testosterone (T) surge of rhesus monkeys reared with their mothers in large outdoor social groups. An early morning basal blood sample was collected at 2.5 months of age, whereas at 5 months samples were collected not only at sunrise, but also at mid-day and sunset to examine the diurnal rhythm of cortisol. At 2.5 months of age sham-operated males exhibited higher cortisol than females, but this sex difference was abolished by neonatal amygdalectomy, with lesioned males also showing lower basal cortisol than controls. Although neonatal amygdalectomy did not alter the postnatal T surge, there was a positive relationship between T and basal cortisol levels. At 5 months of age, neither the sex difference in cortisol, nor its correlation with T levels were apparent any longer. Instead, the diurnal cortisol rhythm of both males and females with amygdalectomy showed a blunted decline from mid-day to sunset compared to controls. These results indicate that neonatal amygdala damage alters basal HPA function in infant rhesus monkeys, affecting males only at early ages (at 2.5 months), while leaving the postnatal T surge intact, and resulting in a flattened diurnal rhythm in both genders at the later ages. Thus, the primate amygdala has a critical influence on the HPA axis in the first few months of life.

The nature of individual differences in inhibited temperament and risk for psychiatric disease: A review and meta-analysis

“…Typically, monkeys display a modulation of fearful, hostile, and defensive behavior across the human intruder paradigm; however, monkeys with neonatal amygdala lesions displayed similar levels of fearful, hostile, and defensive behavior across the conditions (ALN, NEC, and ST) of the human intruder paradigm at two to four months of age (Raper et al, 2013b, 2013c). Neonatal amygdala lesions also resulted in a flattened diurnal cortisol rhythm in monkeys at 5 months of age (Raper et al, 2013a) and blunted cortisol response to stress in young adult monkeys (Raper et al, 2013c). Finally, neonatal amygdala lesions resulted in significantly less freezing in adulthood (Raper et al, 2013c).…”

“…NTRK3 plays a role during development and in adult neuroplasticity, and has been implicated in anxiety disorders (Dierssen et al, 2006); NTRK3 is also downregulated following restraint stress and can be rescued by treatment with a selective-serotonin reuptake inhibitor (fluoxetine) (Barreto et al, 2012). Given findings that alterations in amygdala structure have developmental effects on anxious temperament (Kalin et al, 2001; Machado et al, 2009; Raper et al, 2013a, 2013c), alterations in amygdala neuroplasticity may underlie the development of anxious temperament.…”

“… Note: data from (Fox et al, 2010; Izquierdo and Murray, 2004; Kalin et al, 2007, 2004, 2001; Machado et al, 2009; Machado and Bachevalier, 2008; Raper et al, 2013a, 2013b, 2013c). HPA = hypothalamic-pituitary-adrenal axis; ACTH = adrenocorticotropic hormone; CRF = corticotropin-releasing hormone; ↑ = one study showing a significant increase; - = one study showing no effect; ↓ = one study showing a significant decrease…”

Neonatal amygdala lesions advance pubertal timing in female rhesus macaques

“…The amygdala lesion surgery procedure has been previously described (Raper et al, 2013a). Briefly, subjects and their mothers were removed from the social group and transported to the YNPRC Main Station.…”

“…The location and extent of the lesion was determined by comparing the post-surgical FLAIR images to the pre-surgical images, using the hypersignals from the edema shown on the post-surgical images (Raper et al, 2013a). Using the program Image-J, the surface area of the damage was calculated for each image and multiplied by 1 mm, the thickness of each section, to calculate the volume of damage.…”