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

Ned H. Kalin, MD

Published: March 1, 2003

Article Abstract

Studies of nonhuman primate models have been useful in defining anxious temperament as anindividual’s stable set of physiologic and behavioral responses and in providing insights regardinghuman anxiety. Anxious temperament in rhesus monkeys (Macaca mulatta) is marked by excessiveanxiety, exaggerated defensive behavioral responses, extreme asymmetric right frontal brain electricalactivity, and elevated cerebrospinal fluid levels of corticotropin-releasing hormone and plasmacortisol. In the human brain, extreme asymmetric right frontal activation is likewise associated withnegative affect and anxious disposition. Our studies of infant rhesus monkeys using the human intruderparadigm allow us to investigate individual differences in fear-related defensive behavioralresponses and suggest that responses to threatening stimuli are mediated by γ-aminobutyric acidand benzodiazepine receptors. Ongoing studies with nonhuman primates in our laboratory are furtherexamining the neurochemistry underlying individual differences in anxious temperament. We believethat these studies will provide insights into the adaptive and maladaptive responses of humans as theyrelate to psychopathology as associated with anxiety.

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