Contextual control of the extinction of conditioned fear

Bouton, Mark E.; Bolles, Robert C.

doi:10.1016/0023-9690(79)90057-2

Cited by 749 publications

(733 citation statements)

References 19 publications

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“…For example, when animals first are trained to fear a light CS in context A, then receive extinction training to the light in context B, and finally are tested for fear to the light in either context A or context B, different outcomes are obtained: animals tested in context B (the same context where extinction training took place) exhibit little fear to the light, whereas animals tested in context A exhibit robust fear to the light. 28,32 A similar postextinction return of fear is observed when animals are tested in a third, novel context C following acquisition in context A and extinction in context B. 32,33 The renewal effect is not due to simple context conditioning 28,34 but rather appears to reflect an occasion-setting or modulatory role of context in gating performance to the CS.…”

Section: Behavioral and Theoretical Considerationsmentioning

confidence: 66%

“…28,32 A similar postextinction return of fear is observed when animals are tested in a third, novel context C following acquisition in context A and extinction in context B. 32,33 The renewal effect is not due to simple context conditioning 28,34 but rather appears to reflect an occasion-setting or modulatory role of context in gating performance to the CS. 35 Thus, rather than learning that 'now the cue is no longer paired with the shock', the animal learns that 'now, in this place, the cue is no longer paired with the shock'.…”

Section: Behavioral and Theoretical Considerationsmentioning

confidence: 66%

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Mechanisms of fear extinction

2006

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Excessive fear and anxiety are hallmarks of a variety of disabling anxiety disorders that affect millions of people throughout the world. Hence, a greater understanding of the brain mechanisms involved in the inhibition of fear and anxiety is attracting increasing interest in the research community. In the laboratory, fear inhibition most often is studied through a procedure in which a previously fear conditioned organism is exposed to a fear-eliciting cue in the absence of any aversive event. This procedure results in a decline in conditioned fear responses that is attributed to a process called fear extinction. Extensive empirical work by behavioral psychologists has revealed basic behavioral characteristics of extinction, and theoretical accounts have emphasized extinction as a form of inhibitory learning as opposed to an erasure of acquired fear. Guided by this work, neuroscientists have begun to dissect the neural mechanisms involved, including the regions in which extinction-related plasticity occurs and the cellular and molecular processes that are engaged. The present paper will cover behavioral, theoretical and neurobiological work, and will conclude with a discussion of clinical implications. Molecular Psychiatry (2007) 12, 120-150.

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Section: Behavioral and Theoretical Considerationsmentioning

confidence: 66%

Section: Behavioral and Theoretical Considerationsmentioning

confidence: 66%

Mechanisms of fear extinction

2006

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“…used a renewal design (Bouton and Bolles, 1979) and reported that rats trained to self-administer a heroin-cocaine mixture in one context, context A, and then extinguished in a second, different context, context B, showed a pronounced reinstatement of extinguished drug seeking when tested in context A. This context-induced reinstatement or renewal of extinguished drug seeking has since been reported for a variety of drug rewards including cocaine Fuchs et al, 2007;Hamlin et al, 2008), heroin (Bossert et al, 2004), alcohol Zironi et al, 2006;Hamlin et al, 2007;Marinelli et al, 2007), and nicotine (Diergaarde et al, 2008), as well as the natural reward sucrose (Hamlin et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Lateral Hypothalamus Is Required for Context-Induced Reinstatement of Extinguished Reward Seeking

2009

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We studied the role of lateral hypothalamus (LH) in context-induced reinstatement (renewal) of reward seeking. Rats were trained to respond for 4% (v/v) alcoholic beer or 10% (w/v) sucrose reward in one context (Context A) before extinction training in a second context (Context B). On test, rats were returned to the training context, A (ABA), or the extinction context, B (ABB). Return to the training context (ABA) produced robust reinstatement. Reversible inactivation of LH via baclofen/muscimol infusion prevented context-induced reinstatement of beer and sucrose seeking. This prevention was specific to bilateral infusions into LH. We then used the retrograde neuronal tracer cholera toxin b subunit (CTb) combined with detection of the c-Fos protein to identify activated afferents to LH during contextinduced reinstatement of beer seeking. Double labeling for c-Fos and CTb revealed a significant recruitment of LH-projecting neurons in nucleus accumbens shell (AcbSh) during reinstatement. These afferents could be classified into two anatomically and functionally distinct groups. First, afferents in the ventral AcbSh projecting to LH were activated during reinstatement. Second, afferents in the dorsomedial AcbSh projecting to LH were activated during test in the extinction context. These recruitments were specific to an AcbSh-LH pathway because they were not observed following CTb injection into the immediately adjacent perifornical hypothalamus. These results show that LH is critical for context-induced reinstatement of reward seeking and that parallel striatal-hypothalamic pathways are recruited following return to the training versus extinction contexts.

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“…For example, fear of an extinguished cue typically returns following the presentation of a mild, unsignaled stressor, a phenomenon termed 'reinstatement' (Bouton and Bolles, 1979a). Furthermore, fear typically returns to an extinguished cue when it is presented in a different context to that in which extinction occurred, a phenomenon termed 'renewal' (Bouton and Bolles, 1979b). In addition to providing insight into the behavioral mechanisms underlying extinction, both reinstatement and renewal are recognized as useful laboratory analogs of relapse after exposure therapy.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor-2 Enhances Extinction and Reduces Renewal of Conditioned Fear

Graham

Richardson

2010

Neuropsychopharmacol

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Anxiety disorders are increasingly prevalent in society; hence, there is a need to improve on existing treatments for such disorders. Fibroblast growth factor-2 (FGF2), a mitogen that is involved in brain development and regeneration, has been shown to both facilitate long-term extinction of fear and reduce stress-precipitated relapse in rats. Extinction is the laboratory analog of exposure-based therapies in humans. In this study, we continued to investigate the clinical potential of FGF2 as a pharmacological enhancer of extinction by examining its effect on renewal, a common type of relapse. In all experiments, rats were trained to fear a white noise-conditioned stimulus, and then this learned fear was extinguished the following day. Rats received systemic injections of FGF2 or vehicle immediately after extinction training. At test, on the day after extinction training, levels of freezing elicited by the white noise in either the extinction context or the original training context were measured. FGF2-treated rats showed less renewal of fear when tested in the original training context than did vehicle-treated rats. This pattern occurred even when vehicle rats were given double the amount of extinction training, and when FGF2-treated rats were given equivalent exposure to the extinction context. These results show that FGF2 facilitates long-term extinction and attenuates relapse, and thus highlight its potential as a novel pharmacological adjunct to exposure therapy.

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Contextual control of the extinction of conditioned fear

Cited by 749 publications

References 19 publications

Mechanisms of fear extinction

Mechanisms of fear extinction

Lateral Hypothalamus Is Required for Context-Induced Reinstatement of Extinguished Reward Seeking

Fibroblast Growth Factor-2 Enhances Extinction and Reduces Renewal of Conditioned Fear

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