Phasic vs Sustained Fear in Rats and Humans: Role of the Extended Amygdala in Fear vs Anxiety

In the paper

“chronic fluoxetine decreased stress-induced c-Fos increases in the BNSTL (Bechtholt et al, 2008).”

What the sources say

• Disputed

  The c-Fos Expression Associated with NIH section says novelty tended to decrease c-Fos in the lateral posterolateral bed nucleus of the stria terminalis (STLP), and chronic fluoxetine reversed that change. The Discussion says fluoxetine normalized novelty-inhibited c-Fos in the STLP—the opposite of decreasing a stress-induced rise. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  Checked by a reasoning model — may be wrong.

  cites Bechtholt et al, 2008 sourceExperimental — accuracy not yet measured

In the paper

“Both shock and airpuffs evoke robust and reliable cued fear-potentiated startle (Grillon and Ameli, 1998a; Norrholm et al, 2006).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Grillon and Ameli, 1998a
• Partly supported

  The Abstract reports that pairing a colored-light cue with an airblast produced robust fear-potentiated startle and significant discrimination between cues. Norrholm et al. supports the airpuff portion of the sentence, but our copy does not establish that the effect is reliable across repeated studies or measurements. (LLM, conf=0.82)

  cites Norrholm et al, 2006 sourceExperimental — accuracy not yet measured

In the paper

“a treatment might block context anxiety, not because it was anxiolytic, but because it interfered with a representation of context.”

What the sources say

• Partly supported

  The Results and Discussion (page unavailable) suggest that familiarity with features of a threat situation can alter rats’ defensive behavior, supporting the relevance of how animals perceive a context. The paper does not test a treatment or say that interference with a context representation can reduce context anxiety instead of acting anxiolytically. (LLM, conf=0.78)

  cites Blanchard et al, 1976 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Fanselow, 1986 source

In the paper

“as long-lasting non-associative sensitization also appears to be a BNST-dependent phenomenon (eg, Gewirtz et al, 1998)”

What the sources say

• Supported

  The Results identify the gradual increase in baseline startle as long-term sensitization rather than a conditioned response, and report that BST lesions blocked it. The Conclusion likewise describes a blockade of long-term startle sensitization by BST lesions. Page numbers are not available in the supplied copy. (LLM, conf=0.92)

  cites Gewirtz et al, 1998 source

In the paper

“the PVT is one of the most stress-responsive areas in the brain, based on the induction of a marker of cellar activity, c-Fos, with various stressors”

What the sources say

• Partly supported

  The Discussion identifies the paraventricular nucleus of the thalamus among regions with increased c-Fos expression after conditioned stress and cites reports of its response to unconditioned stressors. It does not establish that the PVT is one of the brain’s most stress-responsive regions relative to other regions. Page numbers are unavailable in our copy. (LLM, conf=0.85)

  cites Beck and Fibiger, 1995 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Bhatnagar and Dallman, 1998 source
• ?Not checked — no full text of the sourcecites Bubser and Deutch, 1999 source

In the paper

“previous findings that electrolytic (Hitchcock and Davis, 1987) or chemical (Campeau and Davis, 1995) CeA lesions, or intra-CeA NBQX infusions (Walker and Davis, 1997b) all blocked fear-potentiated startle to 3.7-s CSs.”

What the sources say

• ?Not checked — no full text of the sourcecites Hitchcock and Davis, 1987 source
• Supported

  The Apparatus section specifies 3.7-second auditory and visual conditioned stimuli. The Concurrent conditioning results report that bilateral ibotenic-acid lesions of the central nucleus completely disrupted fear-potentiated startle to both stimuli. This confirms the chemical-lesion finding attributed to Campeau and Davis; the other interventions in the citing sentence are attributed to other papers. (LLM, conf=0.94)

  cites Campeau and Davis, 1995 source
• Supported

  The Fear-potentiated startle results report that intra-CeA NBQX completely blocked fear-potentiated startle relative to PBS. The Fear-potentiated startle training and testing section specifies a 3.7-second visual conditioned stimulus. The lesion findings have separate citations in the citing sentence; Walker and Davis is cited for the NBQX finding. (LLM, conf=0.94)

  cites Walker and Davis, 1997b source

In the paper

“recent findings from Risbrough et al (2009), as well as from our own laboratory (Walker et al, 2009), indicate a similar and, importantly, preferential involvement of CRF receptors in fear-potentiated startle to context but not discrete fear CSs.”

What the sources say

• Supported

  The Discussion (page not available in our copy) says CRF1 and CRF2 contribute to immediate context-dependent increases in startle. It also reports normal fear-potentiated startle to discrete conditioned cues in receptor-knockout mice and concludes that neither receptor is required for cued fear-potentiated startle. (LLM, conf=0.91)

  cites Risbrough et al (2009) source
• Supported

  The Discussion reports that GSK876008 appeared to disrupt context-potentiated startle in the same rats in which it did not block startle to a 3.7-second discrete conditioned stimulus. The authors caution that they lacked context-discrimination controls, so the context effect could instead reflect shock-induced sensitization; the citing sentence’s ‘indicate’ is consistent with that qualified finding. Our copy supplies section labels but no page numbers. (LLM, conf=0.88)

  cites Walker et al, 2009 source

In the paper

“local infusion of CRF into the CeA failed to increase startle (Liang et al, 1992a)”

What the sources say

• Supported

  The paper’s opening summary states that local CRF infusion into the amygdala did not significantly elevate startle. The discussion says most infusion cannula tips were in the central and basolateral amygdala nuclei, supporting the citing sentence’s reference to the central amygdala, though the result is reported for the infusion group as a whole. (LLM, conf=0.87)

  cites Liang et al, 1992a source

In the paper

“Lee and Davis (1997) confirmed that CeA, but not BNST, lesions disrupted fear-potentiated startle.”

What the sources say

• Supported

  In the section on chemical lesions and fear-potentiated startle, the authors say they tested the animals with CeA or BNST lesions for fear-potentiated startle after testing CRH-enhanced startle. They report that CeA lesions completely blocked fear-potentiated startle, whereas BNST lesions did not affect it. (LLM, conf=0.95)

  cites Lee and Davis (1997) source

In the paper

“infusion of the CRF receptor antagonist α-helical CRF9–41 (αhCRF) into the BNST, but not into the CeA, also blocked CRF-enhanced startle”

What the sources say

• Supported

  The intra-BNST infusion results report that α-hCRH 9-41 significantly reduced CRH-enhanced startle at the higher dose, which the paper describes as a blockade. The intra-CeA infusion results state that the same antagonist did not block CRH-enhanced startle. The supplied passages do not give page numbers. (LLM, conf=0.93)

  cites Lee and Davis (1997) source

In the paper

“chronic or repeated stress of various sorts does increase total (Chappell et al, 1986; Santibanez et al, 2006; Stout et al, 2000) as well as extracellular (Olive et al, 2002) CRF in the BNST of rats.”

What the sources say

• Partly supported

  In the CRF distribution section (page not supplied), the paper reports an approximately 80% rise in BNST CRF-like immunoreactivity after acute and chronic stress, but says it was not statistically significant. This supports a measured increase, not the citing sentence’s unqualified assertion that chronic stress increases total CRF. The extracellular-CRF claim is attributed to a different citation, not to Chappell et al. (LLM, conf=0.88)

  cites Chappell et al, 1986 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Santibanez et al, 2006 source
• ?Not checked — no full text of the sourcecites Stout et al, 2000 source

In the paper

“to have anorectic effects which, in the same study, were not associated with intra-CeA CRF infusions (Ciccocioppo et al, 2003).”

What the sources say

• Supported

  The Histology passage reports that intra-BNST CRF markedly inhibited feeding (Fig. 4A), while the same doses infused into the CeA produced no change in food intake (Fig. 4B). The comparison was made in food-deprived rats. (LLM, conf=0.94)

  cites Ciccocioppo et al, 2003 source

In the paper

“a CRF antagonist infused into the CeA failed to block CRF-enhanced startle (Lee and Davis, 1997)”

What the sources say

• Supported

  The Results section, “Effects of intra-CeA infusion of 6 µg of α-hCRH 9-41 on CRH-enhanced startle,” states that the antagonist infused into the central amygdala did not block the startle-enhancing effect of intracisternal CRH. The discussion likewise says that infusion into the CeA did not significantly attenuate CRH-enhanced startle. (LLM, conf=0.95)

  cites Lee and Davis, 1997 source

In the paper

“Liang et al (1992a) reported that electrolytic lesions of the CeA blocked CRF-enhanced startle when CRF was infused intraventricularly.”

What the sources say

• Supported

  The Surgery section describes bilateral central-amygdala lesions made by passing current through an electrode, consistent with electrolytic lesions. The paper reports that these lesions nearly eliminated the startle enhancement produced by intracerebroventricular (icv) CRF and also describes the effect as blocked. No page number is available for these passages in our copy. (LLM, conf=0.94)

  cites Liang et al (1992a) source

In the paper

“Lee and Davis (1997) identified the BNST as the likely location of the CRF receptors that mediated the increase in startle after CRF is infused i.c.v.”

What the sources say

• Supported

  The Discussion section, “The BNST may be a primary receptor site for CRH given intracerebroventricularly,” explicitly identifies the BNST as a likely receptor site for CRH’s excitatory effect on startle. It also reports that BNST lesions blocked CRH-enhanced startle and that a CRH antagonist infused into the BNST blocked it dose-dependently. (LLM, conf=0.94)

  cites Lee and Davis (1997) source

In the paper

“intra-BNST CRF infusions have also been found to elicit anxiety-associated behaviors in the elevated plus-maze and social interaction tests (Lee et al, 2008; Sahuque et al, 2006)”

What the sources say

• Partly supported

  In Experiment 2, repeated intra-BNST injections of the CRF receptor agonist Ucn1 produced anxiety-like behavior in the social interaction test but not the elevated plus-maze. The Discussion likewise reports no elevated plus-maze effect in this study and attributes that finding to Sahuque et al.; Lee et al. also infused Ucn1 rather than CRF itself. (LLM, conf=0.90)

  cites Lee et al, 2008 sourceExperimental — accuracy not yet measured
• Partly supported

  The Results report that intra-BNST CRF infusion increased anxiety-like behavior in rats in the elevated plus-maze. The paper reports conditioned place aversion as its other behavioral paradigm, not a social interaction test; that part of the claim is unsupported by this source. (LLM, conf=0.88)

  cites Sahuque et al, 2006 sourceExperimental — accuracy not yet measured

In the paper

“to produce conditioned place aversion to places associated with CRF infusion (Sahuque et al, 2006)”

What the sources say

• Supported

  The Results report that 1.0 nmol of CRF infused into the BNST significantly reduced rats’ preference for the CRF-paired compartment. The Discussion explicitly describes intra-BNST CRF administration as producing conditioned place aversion. (LLM, conf=0.95)

  cites Sahuque et al, 2006 source

In the paper

“Liang et al (1992a) had previously shown that intra-amygdala CRF infusions, in contrast to intra-BNST CRF infusions, did not increase startle.”

What the sources say

• Partly supported

  The local-infusion results (page not provided) report that intra-amygdala CRF did not produce a pronounced increase in startle, although some doses caused small, transient increases. Our copy does not report CRF infusion into the BNST or the claimed contrast with it; its BNST mention concerns incidental lesion damage. (LLM, conf=0.88)

  cites Liang et al (1992a) sourceExperimental — accuracy not yet measured

In the paper

“CRF receptor protein and mRNA are abundant in the BNST—much more so than in the CeA (Ju et al, 1989; Potter et al, 1994; Van Pett et al, 2000; Wynn et al, 1984).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Ju et al, 1989
• Partly supported

  The indexed copy describes prominent CRF receptor mRNA expression in septal-region and amygdalar structures (abstract; page not specified). It does not identify the BNST or CeA, compare their abundance, or report receptor protein abundance, so those parts of the claim are unsupported. (LLM, conf=0.75)

  cites Potter et al, 1994 sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites Van Pett et al, 2000 source

In the paper

“intra-BNST CRF infusions mimicked the effect of intra-ventricular infusions.”

What the sources say

• Supported

  The section on intra-BNST and intra-hippocampus CRH infusions reports that intra-BNST CRH increased acoustic startle, as intraventricular CRH did. It also notes differences: the intra-BNST effect was smaller and began sooner, but the claim does not assert that the effects were identical. (LLM, conf=0.91)

  cites Lee and Davis (1997) source

In the paper

“muscimol infused into the BNST decreased social defeat in hamsters, a long-lasting form of sustained anxiety dependent on both the amygdala and the BNST (Markham et al, 2009)”

What the sources say

• Partly supported

  The Results for Experiment 2 and the Discussion report that BNST muscimol reduced the expression of conditioned defeat—submissive and defensive behavior during later testing—not the initial social defeat. The Discussion describes sustained anxiety as a possibility, rather than establishing conditioned defeat as a long-lasting form of it. It also reports different roles for the BNST and amygdala, so the claim's unqualified statement that this form of anxiety depends on both goes beyond the findings. Page numbers were not provided in the passages. (LLM, conf=0.86)

  cites Markham et al, 2009 sourceExperimental — accuracy not yet measured

In the paper

“as well as sustained freezing in response to the odor of fox feces, a rodent predator (Fendt et al, 2003).”

What the sources say

• Partly supported

  The Results (‘Injections of muscimol into the BNST’; page unavailable) report that BNST muscimol blocked the increase in freezing during TMT presentation. The Introduction identifies TMT as a component of fox-feces odor, but the experiment presented TMT rather than the complete odor of fox feces; that distinction is not preserved in the claim. (LLM, conf=0.83)

  cites Fendt et al, 2003 sourceExperimental — accuracy not yet measured

In the paper

“midazolam reduced c-Fos activation in the BNST (McGregor et al, 2004)”

What the sources say

• Partly supported

  Table 1 (Overview of regional Fos expression; page not provided) shows that midazolam reduced cat odor-induced Fos expression in the medial anterior BNST. But the Extended amygdala section reports that midazolam by itself increased Fos expression in the dorsal lateral BNST. The unqualified claim does not distinguish these regions or conditions. (LLM, conf=0.88)

  cites McGregor et al, 2004 sourceExperimental — accuracy not yet measured

In the paper

“Similar results have been reported in PTSD (Grillon et al, 1996; Morgan et al, 1995a, b).”

What the sources say

• Supported

  The Results (§3.2; page unavailable) report significantly reduced prepulse inhibition in Vietnam veterans with PTSD compared with civilian controls, though not significantly compared with combat controls. The citing sentence does not specify what “similar results” refers to, but the paper does report this PTSD finding. (LLM, conf=0.82)

  cites Grillon et al, 1996 source
• ?Not checked — no full text of the sourcecites Morgan et al, 1995a, b source

In the paper

“In a subsequent study in which fear conditioning was carried out off-drug 1 day before the administration of SSRIs, acute citalopram or fluoxetine also facilitated the expression of conditioned fear”

What the sources say

• Supported

  The Introduction states that rats were fear-conditioned drug-free and injected with an SSRI the next day before testing. The Results report that acute citalopram and fluoxetine each increased conditioned fear expression. (LLM, conf=0.95)

  cites Burghardt et al, 2007 source

In the paper

“These studies have reported that internalizing disorders are made up of two sub-dimensions, one representing ‘fear’ diagnoses (eg, simple phobia, social phobia, agoraphobia, panic disorder) and the other ‘anxiety–misery’ diagnoses (depression, dysthymia, GAD, PTSD).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Kruger et al, 1988
• ?Not checked — no full text of the sourcecites Vollebergh et al, 2001 source
• Supported

  The Introduction describes two internalizing factors, fear and anxious-misery, and identifies the phobic and panic diagnoses on the former and depression, dysthymia, and GAD on the latter. The Results report that this population-based factor analysis replicated that structure and that PTSD loaded most strongly on anxious-misery. Passage page numbers are not supplied. (LLM, conf=0.94)

  cites Cox et al, 2002 source

In the paper

“14 days of chronic treatment selectively reduced contextual anxiety but not cued fear (Grillon et al, 2009a).”

What the sources say

• Supported

  The Discussion states that two weeks of citalopram reduced contextual anxiety without affecting cued fear. The Methods (Procedure) specifies that participants took citalopram or placebo daily for 14 days before the second test. (LLM, conf=0.95)

  cites Grillon et al, 2009a source

In the paper

“This interpretation is consistent with our observation that mildly aversive stimuli do not induce contextual anxiety (Grillon et al, 2004, 2009b).”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2004 source
• Partly supported

  The Discussion reports that the less noxious stimuli did not produce contextual startle potentiation in healthy controls or the GAD group. But it also reports heightened contextual anxiety in the PTSD group, so the unqualified claim that mildly aversive stimuli do not induce contextual anxiety is too broad. Page numbers were not available in our copy. (LLM, conf=0.88)

  cites Grillon et al, 2009b sourceExperimental — accuracy not yet measured

In the paper

“fearful subjects show significantly enhanced fear-potentiated startle compared with non-fearful participants when looking at pictures of phobic stimuli (Hamm et al, 1991a; Sabatinelli et al, 2001), when asked to imagine the content of previously seen pictures (Schupp et al, 1997), or to imagine a previously heard or memorized emotional script (Cook et al, 1991; Cuthbert et al, 2003; Vrana and Lang”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Hamm et al, 1991a
• ?Not checked — no full text of the sourcecites Sabatinelli et al, 2001 source
• Partly supported

  The Blink Magnitude results (p. 4) report larger startle blinks while participants imagined previously viewed unpleasant pictures than pleasant pictures. But the Participants section (p. 2) describes psychology-course volunteers, not fearful and non-fearful groups; the paper does not establish the claimed between-group difference. The phobic-picture viewing and emotional-script clauses are attributed to other citations in the citing sentence. (LLM, conf=0.88)

  cites Schupp et al, 1997 sourceExperimental — accuracy not yet measured

In the paper

“Social phobics with circumscribed fear restricted to performance contexts exhibit defensive responses similar to those of simple phobics, in which they show elevated fear of their personal fears but not of standard fears (McTeague et al, 2009).”

What the sources say

• Partly supported

  The Results and Discussion (Social Phobia Subtypes; page not provided) show that patients with circumscribed performance phobia had heightened defensive responses to their personal fear imagery, but not to standard social threats. The paper compares them with controls, not with simple phobics, so the stated similarity to simple phobics is not established by our copy. (LLM, conf=0.83)

  cites McTeague et al, 2009 sourceExperimental — accuracy not yet measured

In the paper

“In contrast, individuals with generalized social phobia show a range of elevated fear that extends beyond their personal fears to more generally shared fears (McTeague et al, 2009).”

What the sources say

• Supported

  The Discussion (Social Phobia Subtypes; page not provided) reports that patients with generalized social phobia responded strongly to both personal and standard social threats, and also showed a substantial response to survival threats. The Results (Social Phobia Subtypes; page not provided) describe fear potentiation across all fear contents, supporting the claimed range beyond personal fears. (LLM, conf=0.89)

  cites McTeague et al, 2009 source

In the paper

“In rats, exaggerated startle levels before a traumatic stressor increased risk of developing PTSD-like symptoms after the stressor (Rasmussen et al, 2008).”

What the sources say

• Supported

  The Discussion reports that rats with higher pre-existing acoustic startle were predisposed to a persistent PTSD-like response after traumatic stress and contextual reminders. The reported results also show that only the high-pre-treatment-startle subgroup developed a further persistent increase in startle after stress and reminders. (LLM, conf=0.94)

  cites Rasmussen et al, 2008 source

In the paper

“Third, the magnitude of phasic fear-potentiated startle is generally larger for a verbal threat. For example, we have shown that startle magnitude can be doubled during verbal threat (Grillon et al, 1991, 1993a, b), whereas we and others have reported startle potentiation of <50% during fear conditioning paradigms (Baas et al, 2004; Lipp et al, 1994, 2003), although it can be higher in certain”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 1991 source
• ?Not checked — no full text of the sourcecites Baas et al, 2004 source

In the paper

“In each case, the startle reflex is enhanced when evoked in the presence of the cue that predicts the shock.”

In the paper

“Light-enhanced startle was reduced selectively by both benzodiazepine (ie, chlordiazepoxide) and non-benzodiazepine (ie, flesinoxan, buspirone, and propranolol) anxiolytics (de Jongh et al, 2002; Walker and Davis, 1997a, 2002a).”

What the sources say

• ?Not checked — no full text of the sourcecites de Jongh et al, 2002 source
• ?Not checked — no full text of the sourcecites Walker and Davis, 1997a source
• ?Not checked — no full text of the sourcecites Walker and Davis, 2002a source

In the paper

“BLAc fibers that project to the BNSTL go right through the CeA (Figure 7).”

In the paper

“However, the interesting point for this discussion on sustained fear is that the level of fear is typically greater to the context in the unpaired than in the paired group. That is, context conditioning is greater in the unpaired group, a finding that is exactly predicted by contemporary learning theory.”

In the paper

“As expected, startle was significantly potentiated by the light in the paired context condition only, reflecting cued phasic fear.”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2006a source

In the paper

“startle amplitude was highest during the first minute”

In the paper

“During shock anticipation, context-potentiated startle is greater in the unpredictable context compared with that in the predictable context (Figure 2).”

In the paper

“We have also found this effect in rhesus monkeys that underwent a brief separation from their mothers during development (Parr et al, 2002).”

What the sources say

• ?Not checked — no full text of the sourcecites Parr et al, 2002 source

In the paper

“These results suggest that context conditioning measured with acoustic startle amplitude should be greater after temporally unpredictable shocks compared with predictable shocks in humans, and this is exactly what we found (Grillon and Davis, 1997).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Grillon and Davis, 1997

In the paper

“Consistent with the animal data, context conditioning was found to be greater in the unpredictable context compared with that in the no shock and predictable contexts (Figure 4).”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2006a source

In the paper

“We also found evidence of CRF receptor involvement in context-potentiated startle using pre-test infusions of the selective CRF1 antagonist GSK876008.”

In the paper

“inactivation of the BLA also blocks CRF-enhanced startle, similar to light-enhanced startle”

In the paper

“we found that lesions of the CeA, but not the BNSTL, blocked fear-potentiated startle, in this case to a 3.7-s light that had been previously paired with footshock”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Hitchcock and Davis, 1986, 1991

In the paper

“we previously found that oral administration of this drug did not disrupt fear-potentiated startle to a 3.7-s light (Figure 12).”

In the paper

“both fear-potentiated and light-enhanced startle were blocked by inactivation of the BLA”

In the paper

“in control and low-dose rats, the effects on fear-potentiated startle to the 3.7-s visual CS were not occluded by pre- to post-shock startle increases, but were instead cumulative with these increases”

In the paper

“Control and low-dose rats did indeed show increased ‘baseline’ startle that was roughly comparable in magnitude with fear-potentiated startle to the explicit 3.7-s visual CS.”

In the paper

“fear-potentiated startle to a 3.7-s visual CS was occluded by co-presentation of a 3.7-s auditory CS in rats that had previously been fear conditioned to both”

In the paper

“The BLA sends heavy projections to both the CeA and the BNST (Figure 7).”

In the paper

“we have now found that local infusion of CGRP into the CeA causes dose-dependent enhancement of startle amplitude”

In the paper

“Table 2 shows that CRF antagonists infused into the CeA did not affect phasic or sustained fear.”

In the paper

“CRF infused into the BLA has no effect on startle by itself.”

In the paper

“In contrast, infusion of the same compounds into the BNST blocked both sustained fear conditioned to long-duration cues and CRF-enhanced startle.”

In the paper

“Figure 15 shows that infusion of a cocktail of NBQX and muscimol into the BLA totally blocked CRF-enhanced startle”

In the paper

“acute administration of allopregnanolone markedly reduced CRF-enhanced startle (Figure 16, left panel), indicating a blockade of sustained fear.”

In the paper

“chronic administration of a progesterone analog that binds to the progesterone receptor but is not metabolized to allopregnanolone had no effect.”

In the paper

“this same treatment had no effect on phasic fear measured fear-potentiated startle to a short-duration visual stimulus (Figure 16, right panel).”

In the paper

“testosterone had no effect on phasic fear-potentiated startle (Toufexis et al, 2004, 2005) (Figure 17, right panel).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Toufexis et al, 2004, 2005

In the paper

“chronic progesterone had the same effect without estrogen priming”

In the paper

“but not to a 3.7-s clicker paired with footshock (Miles and Davis, unpublished observations).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Miles and Davis, unpublished observations

In the paper

“Neither alprazolam nor diphenhydramine affected cued fear-potentiated startle in the predictable condition (Figure 18, left panel).”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2006c source

In the paper

“we now have evidence that 21 days of oral administration of fluoxetine, but not acute administration, blocks the expression of sustained fear to an 8-min clicker (P<0.02)”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Miles and Davis, unpublished observations

In the paper

“In contrast, the sustained increase in startle in the predictable and unpredictable conditions was reduced significantly by the high dose of alprazolam.”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2006c source

In the paper

“although it did block fear-potentiated startle to a 3.7-s clicker (L.A. Miles and M. Davis, unpublished data).”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites L.A. Miles and M. Davis, unpublished data

In the paper

“we have now found that buspirone fails to block sustained fear to an 8-min clicker paired with shock”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites L.A. Miles and M. Davis, unpublished data

In the paper

“This linear increase was less steep with the high-dose alprazolam treatment”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2006c source

In the paper

“In the first session, under no stressful condition, baseline startle in Vietnam veterans with PTSD did not differ from controls.”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 1998c source

In the paper

“startle magnitude during the inter-trial interval (reflecting sustained fear in each condition) increased linearly from the no shock, to the predictable shock, to the unpredictable shock condition in the placebo group.”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 2006c source

In the paper

“Here again, phasic fear measured with fear-potentiated startle reached normative levels in the PTSD veterans (Grillon et al, 1998c).”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 1998c source

In the paper

“The GAD group also showed normative levels of cued fear-potentiated startle.”

In the paper

“Replicating previous findings, we found that the magnitude of phasic fear measured with cued fear-potentiated startle was equivalent in the PTSD and panic disorder patients and in the controls.”

In the paper

“The GAD group did not show abnormal contextual modulation of startle.”

In the paper

“In fact, GAD patients showed affective responses to the threat cue and the context that were indistinguishable from controls.”

In the paper

“In the second, more stressful session that involved the administration of shock, startle was elevated throughout the experiment in the PTSD group (Grillon et al, 1998c).”

What the sources say

• ?Not checked — no full text of the sourcecites Grillon et al, 1998c source

In the paper

“Sustained fear is also mediated by the amygdala, which releases corticotropin-releasing factor, a stress hormone that acts on receptors in the bed nucleus of the stria terminalis (BNST), a part of the so-called ‘extended amygdala.’”

In the paper

“Unlike most traditional psychophysiological measures (eg, heart rate, skin conductance) of emotion, startle increases are typically sensitive to valence and not simply arousal (Lang et al, 2000).”

What the sources say

• ?Not checked — no full text of the sourcecites Lang et al, 2000 source

In the paper

“The peptide corticotropin-releasing factor (CRF) has a special role in sustained fear.”

In the paper

“In humans, symptoms of clinical anxiety are better detected in sustained rather than phasic fear paradigms.”

• Also stated in: § Introduction · plain

  “Finally, clinical symptoms of several anxiety disorders can be modeled more accurately with sustained rather than phasic fear tests.”

In the paper

“Rodent studies suggest that phasic fear is mediated by the amygdala, which sends outputs to the hypothalamus and brainstem to produce symptoms of fear.”

In the paper

“The amygdala and BNST send outputs to the same hypothalamic and brainstem targets to produce phasic and sustained fear, respectively.”

In the paper

“Verbal instruction experiments mimic the mode of communication of danger typically involved in everyday life, without direct experience with the aversive event (eg, one fears and avoids swimming in shark-infested waters not because one has been bitten by a shark, but because one has been forewarned of the risk; Olsson and Phelps, 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Olsson and Phelps, 2007 source

In the paper

“First, as the anticipation of shock is dependent on verbal instruction rather than actual CS–US pairing, the shock itself may not be required at all.”

In the paper

“In rats, sustained fear is more sensitive to anxiolytic drugs.”

• Also stated in: § Introduction · plain

  “Pharmacological analyses of these defensive behaviors show that anxiety is sensitive to anxiolytic drugs, whereas fear is not (Blanchard et al, 1993).”

What the sources say

• ?Not checked — no full text of the sourcecites Blanchard et al, 1993 source

In the paper

“Most importantly, rodent studies suggest that phasic and sustained fear are mediated by similar, highly inter-related, yet importantly different, neural substrates.”

In the paper

“These two states may map onto two distinct clinical entities: one characterized by elevated cued-fear reactivity (eg, phobias) and the other by pervasive anxious apprehension (Kruger et al, 1999;”

What the sources say

• ?Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  cites Kruger et al, 1999
• ?Not checked — no full text of the sourcecites Vollebergh et al, 2001 source

In the paper

“Data based on heart rate as a measure of emotion suggest that darkness is more anxiogenic in individuals with panic disorder than in healthy controls (Melzig et al, 2007).”

What the sources say

• ?Not checked — no full text of the sourcecites Melzig et al, 2007 source

In the paper

“Second, verbal instructions eliminate the potential confound of inter-individual variability in associative learning that occurs during conditioning.”

In the paper

“infusions of CRF into the lateral cerebral ventricle markedly increased the amplitude of the acoustic startle response in rats (CRF-enhanced startle).”

What the sources say

• ?Not checked — no full text of the sourcecites Swerdlow et al, 1986 source

In the paper

“These results show that, given the appropriate aversive stimulus, the verbal threat of predictable and unpredictable US is a reliable paradigm to explore cued fear and contextual anxiety, providing a useful tool for extending research into the clinical domain.”

In the paper

“CRF-positive neurons in the CeAL and dorsal BNSTL express glucocorticoid receptors”

What the sources say

• ?Not checked — no full text of the sourcecites Cintra et al, 1987 source
• ?Not checked — no full text of the sourcecites Honkaniemi et al, 1992 source
• ?Not checked — no full text of the sourcecites Lechner and Valentino, 1999 source

In the paper

“Another way to produce a sustained level of fear is to make an aversive event unpredictable.”

In the paper

“fear was maintained for the duration of the CS during testing (8 min) because the rats could not predict in advance when the CS would end and when the US would occur.”

In the paper

“Although CeAL neurons stain for various neuropeptide transmitters, these same peptides are largely absent from CeAM neurons”

What the sources say

• ?Not checked — no full text of the sourcecites Cassell et al, 1986 source
• ?Not checked — no full text of the sourcecites Day et al, 1999 source
• ?Not checked — no full text of the sourcecites Gray and Magnusson, 1987 source

In the paper

“sustained high-frequency activation may favor the release of CRF.”

In the paper

“Using freezing as a measure of fear, it would not be possible to determine whether this was a performance effect on freezing per se or a reduction of fear because rats only freeze in a state of fear; hence, these control groups would not be informative.”

In the paper

“these findings, by either interpretation, would count as yet another example of BNST-dependent long-duration startle increases susceptible to CRF-R1 blockade.”

In the paper

“these data indicate that the BNST does indeed have an important role in the expression of conditioned fear responses, provided those responses are maintained for a relatively long time.”

In the paper

“As our study used USs distributed throughout the CS, interpretation by Waddell et al (2006) would not seem to account for our data.”

In the paper

“Overall, there is good evidence from several recent studies that an intact and functional BNST is required for context fear expression.”

In the paper

“local infusion of muscimol, a GABA agonist, into the BNST increases fear-potentiated startle to a short-duration cue”

What the sources say

• ?Not checked — no full text of the sourcecites Meloni et al, 2006 source

In the paper

“BNST lesions disrupted conditioned suppression (ie, of bar pressing for food) to a 10-min, but not 1-min clicker CS.”

What the sources say

• ?Not checked — no full text of the sourcecites Waddell et al (2006) source

In the paper

“the hypothesis that short and longer duration fear states are mediated by independent systems”

In the paper

“These results are consistent with the idea that the BNST selectively mediates sustained fear responses.”

In the paper

“rats selectively bred for high levels of context-elicited freezing also show higher than normal levels of fear-potentiated startle to a discrete fear CS.”

What the sources say

• ?Not checked — no full text of the sourcecites Ponder et al, 2007 source

In the paper

“we wondered whether CRF itself might mediate sustained fear. Several lines of evidence suggest this is true.”

In the paper

“Both of these observations may reflect the tonic inhibition of phasic fear by the BNST.”

In the paper

“There is also evidence that CRF is involved in context conditioning.”

What the sources say

• ?Not checked — no full text of the sourcecites Deak et al, 1999 source
• ?Not checked — no full text of the sourcecites Hikichi et al, 2000 source
• ?Not checked — no full text of the sourcecites Kalin and Takahashi, 1990 source

In the paper

“Shortly thereafter, inputs to the CeAL then release CRF into the BNST to cause a long-lasting sustained fear reaction.”

In the paper

“The involvement of BNST CRF receptors in anxiety-associated behaviors is not limited to startle increases, but appears to reflect a more general involvement in anxiety itself (Sakaguchi et al, 1984).”

What the sources say

• ?Not checked — no full text of the sourcecites Sakaguchi et al, 1984 source

In the paper

“such a response would be expected if phasic and sustained startle increases are mediated by different systems”