Skip to main content Accessibility help
×
Hostname: page-component-848d4c4894-5nwft Total loading time: 0 Render date: 2024-04-30T19:15:25.605Z Has data issue: false hasContentIssue false

4 - Mechanisms of Fear Extinction: Toward Improved Treatment for Anxiety

Published online by Cambridge University Press:  27 July 2009

Mark Barad
Affiliation:
Associate Professor Psychiatry and Behavioral Sciences, University of California, Los Angeles
Christopher K. Cain
Affiliation:
Postdoctoral Fellow Center for Neural Science, New York University
Laurence J. Kirmayer
Affiliation:
McGill University, Montréal
Robert Lemelson
Affiliation:
University of California, Los Angeles
Mark Barad
Affiliation:
University of California, Los Angeles
Get access

Summary

INTRODUCTION

Extinction is the explicit model for the treatment of human anxiety disorders by behavior and cognitive behavior therapy (Craske, 1999). These therapies depend crucially on deliberate exposure to cues that generate fear or anxiety in patients in order to reduce gradually the amount of distress such cues cause when encountered during the course of the patient's usual activities, and they are extremely effective. They are also based directly on scientific studies of extinction. The first to use such a protocol for a human subject was Mary Cover Jones in 1924. Jones's successful treatment of little Peter, a two-year-old boy with phobias of rabbits, dogs, cats, stuffed animals, and even of shawls, was inspired by Pavlov's extinction of conditioned salivary responses in dogs (Jones, 1924). Later, Joseph Wolpe based his gradual desensitization method of behavior therapy on his own experiments on fear-conditioned cats (Wolpe, 1969). Wolpe's model of behavior therapy remains in active and successful use to this day.

Nevertheless, although behavior therapy is effective, it still suffers from the limitations of all forms of psychotherapy. That is, it is slow, it requires great effort from the patient and therapist, and it does not always work. Even when it does work, patients remain subject to relapses. These drawbacks are only intensified in the context of PTSD, which is notoriously difficult to treat (McFarlane, 1994).

Type
Chapter
Information
Understanding Trauma
Integrating Biological, Clinical, and Cultural Perspectives
, pp. 78 - 97
Publisher: Cambridge University Press
Print publication year: 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bailey, C. H., Bartsch, D., & Kandel, E. R. (1996). Toward a molecular definition of long-term memory storage. Proceedings of the National Academy of Sciences of the United States of America, 93(24), 13445–13452.CrossRefGoogle Scholar
Baker, J. D., & Azorlosa, J. L. (1996). The N-methyl d-aspartate (receptors) antagonist MK-801 blocks the extinction of Pavlovian fear conditioning. Behavioral Neuroscience, 110(3), 618–620.CrossRefGoogle Scholar
Barad, M., Blouin, A. M., & Cain, C. K. (2004). Like extinction, latent inhibition of conditioned fear in mice is blocked by systemic inhibition of L-type voltage-gated calcium channels. Learning & Memory, 11, 536–539.CrossRefGoogle ScholarPubMed
Barela, P. B. (1999). Theoretical mechanisms underlying the trial-spacing effect in Pavlovian fear conditioning. Journal of Experimental Psychology: Animal Behavioral Processes, 25(2), 177–193.Google ScholarPubMed
Bauer, E. P., Schafe, G. E., & LeDoux, J. E. (2002). N-methyl d-aspartate (receptors) receptors and L-type voltage-gated calcium channels contribute to long-term potentiation and different components of fear memory formation in the lateral amygdala. Journal of Neuroscience, 22(12), 5239–5249.CrossRefGoogle ScholarPubMed
Baum, M. (1988). Spontaneous recovery from the effects of flooding (exposure) in animals. Behaviour Research and Therapy, 26(2), 185–186.CrossRefGoogle Scholar
Baum, M., Andrus, T., & Jacobs, W. J. (1990). Extinction of a conditioned emotional response: Massed and distributed exposures. Behaviour Research and Therapy, 28(1), 63–68.CrossRefGoogle ScholarPubMed
Birch, D. (1965). Extended training extinction effect under massed and spaced extinction trials. Journal of Experimental Psychology, 70, 315–322.CrossRefGoogle Scholar
Bouton, M. E., Kenney, F. A., & Rosengard, C. (1990).State-dependent fear extinction with two benzodiazepine tranquilizers. Behavioral Neuroscience, 104(1), 44–55.CrossRefGoogle ScholarPubMed
Bouton, M. E., & King, D. A. (1983).Contextual control of the extinction of conditioned fear: Tests for the associative value of the context. Journal of Experimental Psychology: Animal Behavioral Processes, 9(3), 248–265.Google ScholarPubMed
Brantigan, C. O., Brantigan, T. A., & Joseph, N. (1982). Effect of beta blockade and beta stimulation on stage fright. American Journal of Medicine, 72(1), 88–94.CrossRefGoogle ScholarPubMed
Bremner, J. D., Krystal, J. H., Southwick, S. M., & Charney, D. S. (1996).Noradrenergic mechanisms in stress and anxiety, II: Clinical studies. Synapse, 23(1), 39–51.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Brown, T. H., Chapman, P. F., Kairiss, E. W., & Keenan, C. L. (1988).Long-term synaptic potentiation. Science, 242(4879), 724–728.CrossRefGoogle ScholarPubMed
Cain, C. K., Blouin, A. M., & Barad, M. (2002). L-type voltage-gated calcium channels are required for extinction, but not for acquisition or expression, of conditioned fear in mice. Journal of Neuroscience, 22(20), 9113–9121.CrossRefGoogle ScholarPubMed
Cain, C. K., Blouin, A. M., & Barad, M. (2003). Temporally massed conditioned stimulus presentations generate more fear extinction than spaced presentations. Journal of Experimental Psychology: Animal Behavior Processes, 29(4), 323–333.Google ScholarPubMed
Cain, C. K., Blouin, A. M., & Barad, M. (2004). Adrenergic transmission facilitates extinction of conditional fear in mice. Learning & Memory, 11(2), 179–187.CrossRefGoogle ScholarPubMed
Campeau, S., Miserendino, M. J., & Davis, M. (1992). Intra-amygdala infusion of the N-methyl-D-aspartate receptor antagonist AP5 blocks acquisition but not expression of fear-potentiated startle to an auditory conditioned stimulus. Behavioral Neuroscience, 106(3), 569–574.CrossRefGoogle ScholarPubMed
Carew, T. J., & Kandel, E. R. (1973).Acquisition and retention of long-term habituation in Aplysia: Correlation of behavioral and cellular processes. Science, 182(117), 1158–1160.CrossRefGoogle ScholarPubMed
Chhatwal, J. P., Davis, M., Maguschak, K. A., & Ressler, K. J. (2005). Enhancing cannabinoid neurotransmission augments the extinction of conditioned fear. Neuropsychopharmacology, 30(3), 516–524.CrossRefGoogle ScholarPubMed
Christie, B. R., & Abraham, W. C. (1994).L-type voltage-sensitive calcium channel antagonists block heterosynaptic long-term depression in the dentate gyrus of anaesthetized rats. Neuroscience Letters, 167(1–2), 41–45.CrossRefGoogle ScholarPubMed
Collingridge, G. L., Kehl, S. J., & McLennan, H. (1983). Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. Journal of Physiology, 334, 33–46.CrossRefGoogle ScholarPubMed
Craske, M. G. (1999). Anxiety disorders: Psychological approaches to theory and treatment. Boulder, CO: Westview Press.Google Scholar
Davis, M. (1992). The role of the amygdala in fear and anxiety. Annual Review of Neuroscience, 15, 353–375.CrossRefGoogle ScholarPubMed
Ebbinghaus, H. (1885/1913). Memory: A contribution to experimental psychology (H. A. Ruger & C. E. Bussenius, Trans.).New York: Teachers College, Columbia University.Google Scholar
Eysenck, H. J. (1968). A theory of the incubation of anxiety/fear responses. Behaviour Research and Therapy, 6(3), 309–321.CrossRefGoogle ScholarPubMed
Falls, W. A., Miserendino, M. J., & Davis, M. (1992). Extinction of fear-potentiated startle: Blockade by infusion of an N-methyl d-aspartate (receptors) antagonist into the amygdala. Journal of Neuroscience, 12(3), 854–863.CrossRefGoogle ScholarPubMed
Fanselow, M. S., DeCola, J. P., & Young, S. L. (1993).Mechanisms responsible for reduced contextual conditioning with massed unsignaled unconditional stimuli. Journal of Experimental Psychology: Animal Behavioral Processes, 19(2), 121–137.Google ScholarPubMed
Fanselow, M. S., & Kim, J. J. (1994).Acquisition of contextual Pavlovian fear conditioning is blocked by application of an N-methyl d-aspartate (receptors) receptor antagonist D,L-2-amino-5-phosphonovaleric acid to the basolateral amygdala. Behavioral Neuroscience, 108(1), 210–212.CrossRefGoogle ScholarPubMed
Fanselow, M. S., & Tighe, T. J. (1988).Contextual conditioning with massed versus distributed unconditional stimuli in the absence of explicit conditional stimuli. Journal of Experimental Psychology: Animal Behavioral Processes, 14(2), 187–199.Google ScholarPubMed
Freudenthal, R., Locatelli, F., Hermitte, G., Maldonado, H., Lafourcade, C., Delorenzi, A., et al.(1998). Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crabChasmagnathus. Neuroscience Letters, 242(3), 143–146.CrossRefGoogle ScholarPubMed
Gale, G., Anagnostaras, S., Godsil, B., Mitchell, S., Nozawa, T., Sage, J., et al.(2004). Role of the basolateral amygdala in the storage of fear memories across the adult lifetime of rats. Journal of Neuroscience, 24, 3810–1815.CrossRefGoogle ScholarPubMed
Gewirtz, J. C., & Davis, M. (1997).Second-order fear conditioning prevented by blocking N-methyl d-aspartate (receptors) receptors in amygdala. Nature, 388(6641), 471–474.CrossRefGoogle ScholarPubMed
Gibbon, J. (1977). Trial and intertrial durations in autoshaping. Journal of Experimental Psychology: Animal Behavior Processes, 3(3), 264–284.Google Scholar
Goelet, P., Castellucci, V. F., Schacher, S., & Kandel, E. R. (1986). The long and the short of long-term memory – a molecular framework. Nature, 322(6078), 419–422.CrossRefGoogle Scholar
Hafner, J., & Milton, F. (1977). The influence of propranolol on the exposure in vivo of agoraphobics. Psychological Medicine, 7(3), 419–425.CrossRefGoogle ScholarPubMed
Hartley, L. R., Ungapen, S., Davie, I., & Spencer, D. J. (1983). The effect of beta adrenergic blocking drugs on speakers' performance and memory. British Journal Psychiatry, 142, 512–517.CrossRefGoogle ScholarPubMed
Hebb, D. O. (1949). The organization of behavior: A neuropsychological theory. New York:Wiley.Google Scholar
Huang, Y. Y., & Malenka, R. C. (1993).Examination of TEA-induced synaptic enhancement in area CA1 of the hippocampus: The role of voltage-dependent Ca2+ channels in the induction of long-term potentiation. Journal of Neuroscience, 13(2), 568–576.CrossRefGoogle Scholar
Huber, K. M., Mauk, M. D., & Kelly, P. T. (1995).Distinct long-term potentiation induction mechanisms: Contribution of N-methyl d-aspartate (receptors) receptors and voltage-dependent calcium channels. Journal of Neurophysiology, 73(1), 270–279.CrossRefGoogle ScholarPubMed
Humphreys, L. (1940). Distributed practice in the development of the conditioned eyelid reaction. Journal of General Psychology, 22, 379–385.CrossRefGoogle Scholar
Jenkins, H. M., Barnes, R. A., & Barrera, J.(1981). Why autoshaping depends on trial spacing. In Locurto, C., Terrace, H. S., & Gibbon, J. (Eds.), Autoshaping and conditioning theory. New York: Academic Press.Google Scholar
Johnston, D., Williams, S., Jaffe, D., & Gray, R. (1992). N-methyl d-aspartate (receptors)-receptor-independent long-term potentiation. Annual Review of Physiology, 54, 489–505.CrossRefGoogle ScholarPubMed
Jones, M. C. (1924). A laboratory study of fear: The case of Peter. Pedagogical Seminary, 31, 308–315.Google Scholar
Josselyn, S. A., Shi, C., Carlezon, W. A., Neve, R. L.Jr, Nestler, E. J., & Davis, M. (2001). Long-term memory is facilitated by cAMP response element-binding protein overexpression in the amygdala. Journal of Neuroscience, 21(7), 2404–2412.CrossRefGoogle ScholarPubMed
Kim, J. J., DeCola, J. P., Landeira-Fernandez, J., & Fanselow, M. S. (1991).N-methyl-D-aspartate receptor antagonist APV blocks acquisition but not expression of fear conditioning. Behavioral Neuroscience, 105(1), 126–133.CrossRefGoogle Scholar
Kogan, J. H., Frankland, P. W., Blendy, J. A., Coblentz, J., Marowitz, Z., Schutz, G., et al. (1997). Spaced training induces normal long-term memory in cAMP-response-element–binding protein mutant mice. Current Biology, 7(1), 1–11.CrossRefGoogle Scholar
Lehmann, J., Colpaert, F., & Canton, H. (1991).Glutamate and glycine co-activate while polyamines merely modulate the N-methyl d-aspartate (receptors) receptor complex. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 15(2), 183–190.CrossRefGoogle ScholarPubMed
Lin, C. H., Yeh, S. H., Leu, T. H., Chang, W. C., Wang, S. T., & Gean, P. W. (2003).Identification of calcineurin as a key signal in the extinction of fear memory. Journal of Neuroscience, 23(5), 1574–1579.CrossRefGoogle ScholarPubMed
Lu, K. T., Walker, D. L., & Davis, M. (2001).Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle. Journal of Neuroscience, 21(16), RC162.CrossRefGoogle ScholarPubMed
Malleret, G., Haditsch, U., Genoux, D., Jones, M. W., Bliss, T. V., Vanhoose, A. M., et al. (2001).Inducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin. Cell, 104(5), 675–686.CrossRefGoogle ScholarPubMed
Marsicano, G., Wotjak, C. T., Azad, S. C., Bisogno, T., Rammes, G., Cascio, M. G., et al.(2002). The endogenous cannabinoid system controls extinction of aversive memories. Nature, 418(6897), 530–534.CrossRefGoogle ScholarPubMed
Martasian, P. J., Smith, N. F., Neill, S. A., & Rieg, T. S. (1992).Retention of massed vs distributed response-prevention treatments in rats and a revised training procedure. Psychological Reports, 70(2), 339–355.CrossRefGoogle Scholar
McFarlane, A. C. (1994). Individual psychotherapy for post-traumatic stress disorder. Psychiatric Clinics of North America, 17(2), 393–408.Google ScholarPubMed
Miserendino, M. J., Sananes, C. B., Melia, K. R., & Davis, M. (1990). Blocking of acquisition but not expression of conditioned fear-potentiated startle by N-methyl d-aspartate (receptors) antagonists in the amygdala. Nature, 345(6277), 716–718.CrossRefGoogle Scholar
Morris, R. G., Anderson, E., Lynch, G. S., & Baudry, M. (1986).Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature, 319(6056), 774–776.CrossRefGoogle ScholarPubMed
Myers, K. M., Ressler, K. J., & Davis, M. (2006). Different mechanisms of fear extinction dependent on length of time since fear acquisition. Learning & Memory, 13(2), 216–223.CrossRefGoogle ScholarPubMed
Newman, M., & Reves, J. G. (1993).Pro: Midazolam is the sedative of choice to supplement narcotic anesthesia. Journal of Cardiothorac and Vascular Anesthesia, 7(5), 615–619.CrossRefGoogle ScholarPubMed
Nicoll, R. A., & Malenka, R. C. (1999).Expression mechanisms underlying N-methyl d-aspartate (receptors) receptor-dependent long-term potentiation. Annals of the New York Academy of Sciences, 868, 515–525.CrossRefGoogle ScholarPubMed
Oler, I. D., & Baum, M. (1968). Facilitated extinction of an avoidance response through shortening of the inter-trial interval. Psychonomic Science, 11, 323–324.CrossRefGoogle Scholar
Pavlov, I. P. (1927). Conditioned reflexes: An investigation of the physiological activity of the cerebral cortex (G. V. Anrep, Trans.).New York: Dover.Google Scholar
Ponnusamy, R., Nissim, H. A., & Barad, M. (2005). Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice. Learning & Memory, 12(4), 399–406.CrossRefGoogle ScholarPubMed
Rescorla, R. A., & Heth, C. D. (1975).Reinstatement of fear to an extinguished conditioned stimulus. Journal of Experimental Psychology: Animal Behavioral Processes, 1(1), 88–96.Google Scholar
Rescorla, R. A., & Wagner, A. R. (1972). A theory of Pavlovian conditioning: Variations in the effectiveness of reinforcement and nonreinforcement. In Black, A. H. & Prokasy, W. F. (Eds.), Classical conditioning II (pp. 64–99).New York:Appleton-Century-Crofts.Google Scholar
Ressler, K. J., Rothbaum, B. O., Tannenbaum, L., Anderson, P., Graap, K., Zimand, E.. (2004). Cognitive enhancers as adjuncts to psychotherapy: Use of d-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry, 61 (11), 1136–1144.CrossRefGoogle Scholar
Reynolds, B. (1945). Extinction of trace conditioned responses as a function of the spacing of trials during the acquisition and extinction series. Journal of Experimental Psychology, 35, 81–95.CrossRefGoogle Scholar
Santini, E., Muller, R. U., & Quirk, G. J. (2001). Consolidation of extinction learning involves transfer from N-methyl d-aspartate (receptors)-independent to N-methyl d-aspartate (receptors)-dependent memory. Journal of Neuroscience, 21(22), 9009–9017.CrossRefGoogle ScholarPubMed
Schafe, G. E., Nadel, N. V., Sullivan, G. M., Harris, A., & LeDoux, J. E. (1999). Memory consolidation for contextual and auditory fear conditioning is dependent on protein synthesis, PKA, and MAP kinase. Learning & Memory, 6(2), 97–110.Google ScholarPubMed
Scharf, M. T., Woo, N. H., Lattal, K. M., Young, J. Z., Nguyen, P. V., & Abel, T. (2002). Protein synthesis is required for the enhancement of long-term potentiation and long-term memory by spaced training. Journal of Neurophysiology, 87(6), 2770–2777.CrossRefGoogle ScholarPubMed
Schiff, R., Smith, N., & Prochaska, J. (1972).Extinction of avoidance in rats as a function of duration and number of blocked trials. Journal of Comparative and Physiological Psychology, 81, 356–359.CrossRefGoogle ScholarPubMed
Sheffield, V. F. (1949). Extinction as a function of partial reinforcement and distribution of practice. Journal of Experimental Psychology, 39, 511–526.CrossRefGoogle Scholar
Shipley, R. H. (1974). Extinction of conditioned fear in rats as a function of several parameters of conditioned stimulus exposure. Journal of Comparative and Physiological Psychology, 87(4), 699–707.CrossRefGoogle Scholar
Stanley, W. C. (1952). Extinction as a function of the spacing of extinction trials. Journal of Experimental Psychology, 43, 249–261.CrossRefGoogle ScholarPubMed
Staubli, U., Thibault, O., DiLorenzo, M., & Lynch, G. (1989). Antagonism of N-methyl d-aspartate (receptors) receptors impairs acquisition but not retention of olfactory memory. Behavioral Neuroscience, 103(1), 54–60.CrossRefGoogle Scholar
Tanaka, M., Yoshida, M., Emoto, H., & Ishii, H. (2000). Noradrenaline systems in the hypothalamus, amygdala and locus coeruleus are involved in the provocation of anxiety: Basic studies. European Journal of Pharmacology, 405(1–3), 397–406.CrossRefGoogle ScholarPubMed
Tang, Y. P., Shimizu, E., Dube, G. R., Rampon, C., Kerchner, G. A., Zhuo, M., et al.(1999). Genetic enhancement of learning and memory in mice. Nature, 401(6748), 63–69.CrossRefGoogle ScholarPubMed
Terrace, H. S., Gibbon, J., Farrell, L., & Baldock, M. D. (1975).Temporal factors influencing the acquisition and maintenance of an autoshaped keypeck. Animal Learning & Behavior, 3(1), 53–62.CrossRefGoogle Scholar
Tully, T., Preat, T., Boynton, S. C., & DelVecchio, M. Vecchio, M. (1994). Genetic dissection of consolidated memory in Drosophila. Cell, 79(1), 35–47.CrossRefGoogle ScholarPubMed
Walker, D. L., Ressler, K. J., Lu, K. T., & Davis, M. (2002). Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. Journal of Neuroscience, 22(6), 2343–2351.CrossRefGoogle ScholarPubMed
Weisskopf, M. G., Bauer, E. P., & LeDoux, J. E. (1999).L-type voltage-gated calcium channels mediate N-methyl d-aspartate (receptors)-independent associative long-term potentiation at thalamic input synapses to the amygdala. Journal of Neuroscience, 19(23), 10512–10519.CrossRefGoogle ScholarPubMed
Westbrook, R. F., Smith, F. J., & Charnock, D. J. (1985). The extinction of an aversion: Role of the interval between non-reinforced presentations of the averted stimulus. Quarterly Journal of Experimental Psychology: Comparative and Physiological Psychology, 37B, 255–273.CrossRefGoogle Scholar
Westra, H. A., & Stewart, S. H. (1998).Cognitive behavioural therapy and pharmacotherapy: Complementary or contradictory approaches to the treatment of anxiety?Clinical Psychology Reviews, 18(3), 307–340.CrossRefGoogle ScholarPubMed
Wigstrom, H., & Gustafsson, B. (1986). Postsynaptic control of hippocampal long-term potentiation. Journal of Physiology, 81(4), 228–236.Google ScholarPubMed
Wolpe, J. (1969). The practice of behavior therapy (1st ed.). New York:Pergamon Press.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×