Effects of bed nucleus of the stria terminalis lesions on conditioned anxiety: Aversive conditioning with long-duration conditional stimuli and reinstatement of extinguished fear.

Abstract

Four experiments investigated the effects of lesions of the bed nucleus of the stria terminalis (BNST) on conditioned fear and anxiety. Though BNST lesions did not disrupt fear conditioning with a short-duration conditional stimulus (CS; Experiments 1 and 3), the lesion attenuated conditioning with a longer duration CS (Experiments 1 and 2). Experiment 3 found that lesions attenuated reinstatement of extinguished fear, which relies on contextual conditioning. Experiment 4 confirmed that the lesion reduced unconditioned anxiety in an elevated zero maze. The authors suggest that long-duration CSs, whether explicit cues or contexts, evoke anxiety conditioned responses, which are dissociable from fear responses to shorter CSs. Results are consistent with behavioral and anatomical distinctions between fear and anxiety and with a behavior-systems view of defensive conditioning.

Models and mechanisms of anxiety: evidence from startle studies

“…It is also not required for freezing to a 20-sec discrete cue, but it is necessary for freezing to context (Sullivan et al 2004). Further, BNST lesions do not affect conditioned suppression of bar-pressing behavior to a 1-min discrete CS but greatly reduces conditioned suppression to a 10-min discrete CS (Waddell et al 2006). However, because in this study BNST lesions were made prior to training it is unclear whether BNST lesions disrupt conditioned fear learning or conditioned fear expression.…”

“…Results mostly based on startle studies show that the CeA, which mediates fear, is activated by discrete cues that signal an aversive event and promote a behavioral response of fight or flight. The BNST is activated by more temporally uncertain (Walker et al 2003) or distal (Waddell et al 2006) threats. This structure is required to maintain the sustained state of anxiety that ensues.…”

“…There is currently not clear response to this question, in part because very few studies have compared the influence of the amygdala and of the BNST on short-and long-duration threat. The BNST is clearly involved in the effect of stressors that last several minute (Sullivan et al 2004;Waddell et al 2006;Walker and Davis 1997a) to hours or days (Bangasser et al 2005;Hammack et al 2004). The earliest time of BNST involvement is unknown.…”

“…Indeed, phasic startle potentiation (i.e., fear-potentiated startle) is obtained in aversive conditioning studies, whereas light-enhanced startle, shock sensitization of startle, and CRH-enhanced startle are unconditioned responses. However, recent studies relying on measures of anxiety other than startle have also demonstrated the role of BNST in sustained forms of aversive conditioning such as context conditioning (Sullivan et al 2004) and long-duration conditioned stimuli (Waddell et al 2006), suggesting that the BNST is involved in sustained aversive states rather than unconditioned responses per se.…”

“…Like context conditioning, long-duration CSs induce a sustained aversive state in rodents that can be blocked by lesions of the BNST (Waddell et al 2006). Long-duration CSs have been rarely used in humans (Lovibond 1992).…”