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Anxiety in non-human primates

Anxiety disorders adversely affect millions of people and account for substantial morbidity in the United States. Anxiety disrupts an individual’s ability to effectively engage and interact in social and non-social situations. The onset of anxiety disorders may begin at an early age or occur in response to life events. Thus, the effects of anxiety are broad ranging, affecting both family and work dynamics, and may limit an individual’s quality of life.

While there has been a great deal of research focused on anxious behavior and anxiety disorders in the past few decades, there is still much we do not know. In order to better understand anxiety disorders, and to develop novel options for those who are nonresponsive to current treatments, scientists need to investigate the biobehavioral mechanisms that underlie the expression of anxiety related behavior. Research with humans subjects is one strategy used to gain insight on how to effectively treat anxiety disorders. However, there are inherent difficulties with such studies, including complex life histories and differences in access to resources (such as health care), as well as ethical issues. Common physiology between humans and other animals allow for the development of animal models that allow scientists to examine the neurobiological underpinnings of anxiety disorders. The non-human primate (NHP) has been used in the study of anxiety due to the physiological, behavioral and neural commonalities we share.

One type of anxiety assessment in non-human primates relies on direct behavioral observations, either in the animal’s ‘home environment’ or in a situation in which the animal is mildly challenged to induce an anxious state. In these procedures, observers typically look for the presence of behaviors indicative of anxiety, including fear and displacement behaviors (normal behaviors that may occur at seemingly inappropriate times). For example, in certain stressful situations, macaques may pick at their hair, a behavior similar to hair twirling in humans. Importantly anxiolytic drugs that reduce the occurrence of these behaviors in humans have been shown to reduce these behaviors in non-human primates, suggesting a common biological mechanism.

One commonly used procedure to assess anxiety in non-human primates is the “Human Intruder Test” (HIT). This procedure was designed to evaluate an animal’s response to the “uncertainty” of the presence of an unfamiliar human. The species appropriate response when presented with this mild challenge is to remain still and vigilant; however, there is a range of responses, with some animals showing little response and others excessive freezing behavior. Variations of this procedure have used similar stimuli, including unfamiliar conspecifics and predatory threats (e.g., stuffed predator) to measure anxiety-related responses. Animals that exhibit heightened anxiety responses in the Human Intruder Test also show alterations in the same neurobiological systems affected in humans with anxiety disorders.

Barbary macaque. CC0 via Pixabay.
Barbary macaque. CC0 via Pixabay.

Another class of anxiety tests in non-human primates relies on measuring physiological response following the presentation of an unexpected auditory or motor stimulus. For example, anxious people are more likely than others to react to a brief, unexpected sound with an exaggerated heart rate. Researchers have adopted similar methodology to assess startle response for nonhuman primates using a wide range of stimuli and physiological parameters.

Other research has focused on the cognitive processes involved in the regulation of anxiety responses. These tests of “cognitive bias” are based on the idea that an individual’s tendency to attend to potentially noxious stimuli tell us something about how the individual processes or weighs the experience. Therefore, an individual’s “anxious” state can be by assessed from his or her judgment about or attention to stimuli with different potentials to evoke anxiety. Cognitive bias procedures have been adapted and successfully employed in humans and other animals with similar response strategies across species, making these tests valuable comparative tools in our understanding of anxious behavior behavior.

Our review presents non-human primate models used by scientists in an effort to understand the biobehavioral mechanisms that mediate anxiety. The cross-species approach of modeling human psychopathology aims to discover targets for treatment toward the goal of reducing human suffering caused by anxiety disorders. Additionally, the knowledge gained from our investigation of anxiety-like behavior inform captive care of non-human primates. The studies reviewed have refined our understanding of factors that may result in anxiety-like behavior and provide information on how to manage them. Modeling psychopathology in non-human primates is necessary and critical to our understanding and treatment of these disorders in humans and nonhuman primates.

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