Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm.

Hitchcock, Janice M.; Davis, Michael J.

doi:10.1037/0735-7044.100.1.11

Cited by 485 publications

(316 citation statements)

References 57 publications

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“…Similar results have been found with a short-duration auditory CS (Campeau and Davis 1995). Post training lesions of the CeA also block fear-potentiated startle to a short-duration CS (Campeau and Davis 1995;Hitchcock and Davis 1986). Contrasting with these results, lesions or inactivation of the BNST do not affect fear-potentiated startle to a short-duration CS (Gewirtz et al 1998;Walker and Davis 1997a).…”

Section: Preclinical Evidence For Dissociated Neural Systems Of Fear supporting

confidence: 79%

“…The earliest time of BNST involvement is unknown. As already indicated, the BNST is not involved in the expression of fearpotentiated startle to CS lasting 3.7 sec (Campeau and Davis 1995;Hitchcock and Davis 1986;Sananes and Davis 1992). 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).…”

Section: Discussionmentioning

confidence: 88%

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Models and mechanisms of anxiety: evidence from startle studies

2007

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Rationale-Preclinical data indicates that threat stimuli elicit two classes of defensive behaviors, those that are associated with imminent danger and are characterized by avoidance or fight (fear), and those that are associated with temporally uncertain danger and are characterized by sustained apprehension and hypervigilance (anxiety).Objective-To 1) review evidence for a distinction between fear and anxiety in animal and human experimental models using the startle reflex as an operational measure of aversive states, 2) describe experimental models of anxiety, as opposed to fear, in humans, 3) examine the relevance of these models to clinical anxiety.Results-The distinction between phasic fear to imminent threat and sustained anxiety to temporally uncertain danger is suggested by psychopharmacological and behavioral evidence from ethological studies and can be traced back to distinct neuroanatomical systems, the amygdala and the bed nucleus of the stria terminalis. Experimental models of anxiety, not fear, are relevant to nonphobic anxiety disorders.Conclusions-Progress in our understanding of normal and abnormal anxiety is critically dependent on our ability to model sustained aversive states to temporally uncertain threat.

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Section: Preclinical Evidence For Dissociated Neural Systems Of Fear supporting

confidence: 79%

Section: Discussionmentioning

confidence: 88%

Models and mechanisms of anxiety: evidence from startle studies

2007

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“…The same pattern was observed for Corticotropin-Releasing Factor Immunoreactivity (CRFir) in the locus coeruleus (also see Ladd et al 1996). Considering the importance of this amygdaloid CRF system in mediating behavioral responses to novelty (Hitchcock and Davis 1986;Liang et al 1992;Krahn et al 1988), we propose that BZ-CRF interactions within the amygdala serve as a critical neural substrate for the behavioral differences in response to novelty observed among H, NH, and MS rats.…”

Section: Discussionsupporting

confidence: 63%

The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat

Caldji

Francis

Sharma

et al. 2000

Neuropsychopharmacology

516

333

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We compared the effects of handling or maternal separation from the day following birth until postnatal day 14 on behavioral responses to novelty and on GABA A and central benzodiazepine (CBZ) receptor levels in the rat. As adults, handled animals showed reduced startle responsivity, increased exploration in a novel open field, and decreased novelty-induced suppression of feeding relative to the handled (H) and/or maternal separation (MS) groups. As compared with handled animals, both nonhandled (NH) and MS animals displayed: (1) reduced GABA A receptor levels in the locus coeruleus (LC) and the n. tractus solitarius (NTS); (2) reduced CBZ receptor sites in the central and lateral n. of the amygdala, the frontal cortex, and in the LC and NTS; and (3) The development of behavioral and endocrine responses to acute stress is greatly influenced by the early postnatal rearing environment (for reviews see Levine 1975;Denenberg 1964;Meaney et al. 1996). These environmental effects persist throughout the life of the animal, resulting in stable individual differences in stress reactivity. Indeed, there is considerable plasticity in the development of these systems. Postnatal handling during the first week of life greatly decreases behavioral fearfulness and hypothalamic-pituitary-adrenal (HPA) responses to stress; whereas, repeated periods of prolonged maternal separation produce enhanced reactivity. Increased stress reactivity has been associated with an enhanced risk for several forms of illness, including affective disorders, diabetes, autoimmune disorders, and coronary heart disease (Chrousos and Gold 1992;Higley et al. 1991;McEwen and Steller 1993;Seckl and Meaney 1994). Thus, in determining the magnitude of behavioral and endocrine responses to stress, early life events NO . 3 contribute to vulnerability to disease in later life (Seckl and Meaney 1994). The critical question, then, concerns the mechanisms for these early environmental effects on the development of behavioral and endocrine responses to stress.Postnatal handling has been shown to decrease fearfulness to novelty (Levine 1962(Levine , 1957Denenberg 1964;Bodnoff et al. 1987). As adults, handled (H) rats show reduced novelty-induced suppression of appetitive behavior and increased exploration in novel environments. The behavioral effects of repeated maternal separation in rats are less documented, although, in primates, there is considerable evidence for enhanced fearfulness in animals exposed to maternal separation in early life (Sackett 1969).The mechanisms underlying these early environmental effects on behavioral responses to novelty are unclear. Bodnoff et al. (1987) reported that neonatal handling increased forebrain central benzodiazepine (CBZ) receptor levels, with no indication of where in the forebrain such differences might exist. Nevertheless, these data are certainly consistent with the wellestablished, anxiolytic effects of benzodiazepines on behavioral responses to novelty (see File 1995 for a review). Moreover, these findings are a...

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“…Whereas SCR is highly sensitive to attentional processes (e.g., Filion, Dawson, Schell, & Hazlett, 1991) and reflects increases in general sympathetic arousal, attentional effects on FPS-though present-may well be smaller than emotional effects (e.g., Bocker, Baas, Kenemans, & Verbaten, 2004) and FPS is more valence specific (for a review, see Lang, Bradley, & Cuthbert, 1998). Additionally, the construct validity of FPS as a measure of fear is supported by the central role played by amygdala-based "fear circuits" in the potentiation of startle in both rodents (e.g., Hitchcock & Davis, 1986) and humans (e.g., Pissiota et al, 2003). Because of these advantages, FPS is increasingly used to measure psychophysiological correlates of pathologic anxiety and to test the anxiolytic properties of pharmaceutical compounds (for a review, see Grillon, in press).…”

Section: Introductionmentioning

confidence: 99%

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

Lissek

Biggs

Rabin

et al. 2008

Behaviour Research and Therapy

338

382

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Though generalization of conditioned fear has been implicated as a central feature of pathological anxiety, surprisingly little is known about the psychobiology of this learning phenomenon in humans. Whereas animal work has frequently applied methods to examine generalization gradients to study the gradual weakening of the conditioned-fear response as the test stimulus increasingly differs from the conditioned stimulus (CS), to our knowledge no psychobiological studies of such gradients have been conducted in humans over the last 40 years. The current effort validates an updated generalization paradigm incorporating more recent methods for the objective measurement of anxiety (fear-potentiated startle). The paradigm employs 10, quasi-randomly presented, rings of graduallyincreasing size with extremes serving as CS+ and CS-. The eight rings of intermediary size serve as generalization stimuli (GS's) and create a continuum-of-similarity from CS+ to CS-. Both startle data and online self-report ratings demonstrate continuous decreases in generalization as the presented stimulus becomes less similar to the CS+. The current paradigm represents an updated and efficacious tool with which to study fear generalization-a central, yet understudied conditioningcorrelate of pathologic anxiety.

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Lesions of the amygdala, but not of the cerebellum or red nucleus, block conditioned fear as measured with the potentiated startle paradigm.

Cited by 485 publications

References 57 publications

Models and mechanisms of anxiety: evidence from startle studies

Models and mechanisms of anxiety: evidence from startle studies

The Effects of Early Rearing Environment on the Development of GABAA and Central Benzodiazepine Receptor Levels and Novelty-Induced Fearfulness in the Rat

Generalization of conditioned fear-potentiated startle in humans: Experimental validation and clinical relevance

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