The Role of the Central Nucleus of the Amygdala in Mediating Fear and Anxiety in the Primate

Abstract

Numerous studies demonstrate that the rhesus monkey is an excellent species with which to investigate mechanisms underlying human emotion and psychopathology. To examine the role of the central nucleus of the amygdala (CeA) in mediating the behavioral and physiological responses associated with fear and anxiety, we used rhesus monkeys to assess the effects of excitotoxic lesions of the CeA. Behavioral and physiological responses of nine monkeys with bilateral CeA destruction (ranging from 46 to 98%) were compared with five animals with asymmetric lesions (42-86.5% destruction on the most affected side) and with 16 unoperated controls. Results suggest that similar to rodent species, the primate CeA plays a role in mediating fear-and anxiety-related behavioral and endocrine responses. Compared with controls and the asymmetric-lesion group, bilaterally lesioned monkeys displayed significantly less fear-related behavior when exposed to a snake and less freezing behavior when confronted by a human intruder. In addition, bilaterally lesioned monkeys had decreased levels of CSF corticotrophin-releasing factor (CRF), and both lesioned groups had decreased plasma ACTH concentrations. In contrast to these findings, patterns of asymmetric frontal brain electrical activity, as assessed by regional scalp EEG, did not significantly differ between control and lesioned monkeys. These findings suggest that in primates, the CeA is involved in mediating fear-and anxiety-related behavioral and pituitary-adrenal responses as well as in modulating brain CRF activity.

Bilateral neurotoxic amygdala lesions in rhesus monkeys (Macaca mulatta): Consistent pattern of behavior across different social contexts.

“…We believe this evidence suggests that heightened affiliative social interactions following amygdala lesions stems from a more general inability to properly perceive danger or threat in the environment and use such information to modulate social behavior adaptively. In line with this view, deficits in threat detection or fear reactivity have been specifically demonstrated for monkeys with bilateral neurotoxic amygdala lesions in both social (Machado & Bachevalier, 2006) and nonsocial settings (Izquierdo, Suda, & Murray, 2005;Kalin, Shelton, & Davidson, 2004;Kalin, Shelton, Davidson, & Kelley, 2001;Mason et al, 2006;Meunier, Bachevalier, Murray, Málková, & Mishkin, 1999). These abnormalities are not restricted to nonhuman primates, since humans with amygdala lesions also demonstrate specific deficits in identifying fearful facial expressions (Adolphs et al, 1999), rating the magnitude of fearful expressions (Adolphs, Tranel, Damasio, & Damasio, 1995) and assessing the approachability or trustworthiness of unfamiliar individuals (Adolphs, Tranel, & Damasio, 1998).…”

Predator threat induces behavioral inhibition, pituitary-adrenal activation and changes in amygdala CRF-binding protein gene expression

“…Since the amygdala mediates adaptive and maladaptive fear and anxiety responses (Blanchard and Blanchard, 1972;LeDoux, 2000;Davis and Whalen, 2001;Amaral, 2003;Kalin et al, 2004), it is of particular importance that ferret exposure increased c-fos expression within various nuclei of the amygdala. Consistent with previous studies using cat odor as a stimulus (Dielenberg et al, 2001;McGregor et al, 2004) we found that 10 min of ferret exposure resulted in a robust increase in the number of Fos-positive cells within the MeA.…”

“…Considerable evidence implicates the amygdala in conditioned and unconditioned fear responses (Blanchard and Blanchard, 1972;LeDoux, 2000;Davis and Whalen, 2001;Amaral, 2003;Kalin et al, 2004), and human functional imaging studies have demonstrated increased amygdala activation in some patients with anxiety and depressive disorders (Drevets, 2003;Rauch et al, 2003). Furthermore, evidence supports a role for the amygdala CRF system in mediating anxiety and fear.…”

Central amygdala nucleus (Ce) gene expression linked to increased trait-like Ce metabolism and anxious temperament in young primates

“…The Ce is of interest because its efferent projections coordinate autonomic, hormonal, behavioral, and emotional responses to stress (20), and Ce lesions in monkeys are sufficient to reduce AT (21). Furthermore, rodent studies demonstrate that direct Ce manipulations markedly alter unconditioned anxiety responses (22), similar to those elicited by novel or potentially threatening situations in children with high AT.…”