Pharmacological and anatomical analysis of fear conditioning using the fear-potentiated startle paradigm

Pharmacological and anatomical analysis of fear conditioning using the fear-potentiated startle paradigm are reviewed. This test measures conditioned fear by an increase in the amplitude of a simple reflex (the acoustic startle reflex) in the presence of a cue previously paired with a shock. This paradigm offers a number of advantages as an alternative to most animal tests of fear or anxiety because it involves no operant and is reflected by an enhancement rather than a suppression of ongoing behavior. Fear-potentiated startle is selectively decreased by drugs such as diazepam, morphine, and buspirone that reduce fear or anxiety clinically. Electrical stimulation techniques suggest that a visual conditioned stimulus ultimately alters acoustic startle at a specific point along the acoustic startle pathway. Relevant visual structures implicated in potentiated startle include the lateral geniculate nucleus, visual cortex, and deep and intermediate layers of the superior colliculus. The central nucleus of the amygdala and the caudal branch of the ventral amygdalofugal pathway projecting to or through the substantia nigra are also necessary for potentiated startle to occur. Electrical stimulation of the central nucleus of the amygdala markedly increases acoustic startle. By combining these behavioral, anatomical, physiological, and pharmacological approaches, it should soon be possible to determine each neural pathway that is required for a stimulus signaling fear to alter startle behavior. Once the exact structures are delineated, it should be possible to determine the neurotransmitters that are released during a state of fear and how this chemical information is relayed along these pathways so as to affect behavior.