Nonhuman Primate Studies of Fear, Anxiety, and Temperament and the Role of Benzodiazepine Receptors and GABA Systems

Studies of nonhuman primate models have been useful in defining anxious temperament as an individual’s stable set of physiologic and behavioral responses and in providing insights regarding human anxiety. Anxious temperament in rhesus monkeys (Macaca mulatta) is marked by excessive anxiety, exaggerated defensive behavioral responses, extreme asymmetric right frontal brain electrical activity, and elevated cerebrospinal fluid levels of corticotropin-releasing hormone and plasma cortisol. In the human brain, extreme asymmetric right frontal activation is likewise associated with negative affect and anxious disposition. Our studies of infant rhesus monkeys using the human intruder paradigm allow us to investigate individual differences in fear-related defensive behavioral responses and suggest that responses to threatening stimuli are mediated by γ-aminobutyric acid and benzodiazepine receptors. Ongoing studies with nonhuman primates in our laboratory are further examining the neurochemistry underlying individual differences in anxious temperament. We believe that these studies will provide insights into the adaptive and maladaptive responses of humans as they relate to psychopathology as associated with anxiety.

J Clin Psychiatry 2003;64(suppl 3):41-44