Role of noradrenergic projections to the bed nucleus of the stria terminalis in neuroendocrine and behavioral responses to fear-related stimuli in rats.

The bed nucleus of the stria terminalis (BNST) receives dense noradrenergic projections from the brainstem and has been claimed to play a role in expression of a variety of stress responses. Fear-related stimuli suppress vasopressin and facilitate oxytocin release from the neurohypophysis and induce behavioral suppression. Here we investigated in male rats whether conditioned fear stimuli increase noradrenergic activity in the BNST and whether depletion of epinephrine content in the BNST prevents neuroendocrine and behavioral responses to fear stimuli. Environmental stimuli previously paired with electric footshocks increased the ratio of 3-methoxy-4-hydroxyphenylglycol to norepinephrine contents in the BNST, suggesting that the stimuli activated noradrenergic projections to the BNST. 5-Amino-2, 4-dihydroxy-alpha-methylphenylethylamine, a neurotoxin relatively selective for noradrenergic fibers, when injected into the BNST 7 days before measurement, decreased the content of norepinephrine by 95% and that of dopamine or serotonin by about 50%. In the rats that received the neurotoxin, the suppressive vasopressin but not the augmentative oxytocin response to intermittent footshocks was abolished. In the experiments with conditioned fear stimuli, the neurotoxin given before training partially but significantly impaired the suppressive vasopressin and behavioral responses to testing stimuli. The neurotoxin given after training, however, did not prevent the vasopressin, oxytocin or behavioral responses. The results suggest that noradrenergic fibers in the BNST mediate the suppressive vasopressin but not the augmentative oxytocin response to nonassociatively applied fear stimuli and that they modulate, in a facilitative fashion, acquisition but not retention or recall of the emotional memory associated with the vasopressin and behavioral responses to conditioned fear stimuli. Copyright 1998 Elsevier Science B.V.