Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear

doi:10.1016/j.neuroscience.2007.03.042

Neuroscience

Volume 146, Issue 4, 8 June 2007, Pages 1495-1503

https://doi.org/10.1016/j.neuroscience.2007.03.042 Get rights and content

Abstract

Fear conditioning and fear extinction play key roles in the development and treatment of anxiety-related disorders, yet there is little information concerning experiential variables that modulate these processes. Here we examined the impact of exposure to a stressor in a different environment on subsequent fear conditioning and extinction, and whether the degree of behavioral control that the subject has over the stressor is of importance. Rats received a session of either escapable (controllable) tail shock (ES), yoked inescapable (uncontrollable) tail shock (IS), or control treatment (home cage, HC) 7 days before fear conditioning in which a tone and foot shock were paired. Conditioning was measured 24 h later. In a second experiment rats received ES, IS or HC 24 h after contextual fear conditioning. Extinction then occurred every day beginning 7 days later until a criterion was reached. Spontaneous recovery of fear was assessed 14 days after extinction. IS potentiated fear conditioning when given before fear conditioning, and potentiated fear responding during extinction when given after conditioning. Importantly, ES potently interfered with later fear conditioning, decreased fear responding during fear extinction, and prevented spontaneous recovery of fear. Additionally, we examined if the activation of the ventral medial prefrontal cortex (mPFCv) by ES is critical for the protective effects of ES on later fear conditioning. Inactivation of the mPFCv with muscimol at the time of the initial experience with control prevented ES-induced reductions in later contextual and auditory fear conditioning.

Finally, we explored if the protective effects of ES extended to an unconditioned fear stimulus, ferret odor. Unlike conditioned fear, prior ES increased the fear response to ferret odor to the same degree as did IS.

Section snippets

Animals

Male Sprague–Dawley rats (300–325 g; Harlan, Indianapolis, IN, USA) were used in all experiments. Rats were housed in pairs on a 12-h light/dark cycle (lights on at 7:00 A.M.). However, in experiment 4 the animals were kept on a reverse light/dark cycle (lights on at 9:00 P.M. and off at 9:00 A.M.). Standard laboratory chow and water were available ad libitum. All rats were allowed to acclimate to colony conditions for 7–10 days prior to experimentation. All experiments were conducted in

Experiment 1: Effect of ES and yoked IS on subsequent contextual and auditory-cued fear conditioning occurring 7 days later

This experiment investigated whether exposure to ES or yoked IS administered in small wheel-turn boxes would alter fear conditioning occurring 7 days later. Thus, rats (n=8/group) were exposed to ES, yoked IS, or HC treatment and 7 days later all subjects received fear conditioning. Fear to the context and to the tone was tested 24 h later. Prior exposure to ES reduced subsequent contextual fear conditioning, whereas prior IS led to a potentiation. Percentage of freezing scores to the context

Discussion

In the present experiments exposure to tail shocks of differing controllability in one environment had bi-directional effects on fear conditioning 7 days later in a different environment. IS potentiated fear conditioning both to the tone and context. These results are consistent with those of Rau et al. (2005) who found that the administration of inescapable grid shocks potentiated later fear conditioning in a different environment. Rau et al. (2005) eliminated a number of interpretations of

Acknowledgments

The authors would like to thank Dr. Jerry Rudy for his insightful comments and discussion. This research was supported by grants MH 050479 (S.F.M.) and MH 075213 (M.V.B.) from the National Institute of Mental Health.

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Behavioural neuroscienceControllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear

Abstract

Section snippets

Animals

Experiment 1: Effect of ES and yoked IS on subsequent contextual and auditory-cued fear conditioning occurring 7 days later

Discussion

Acknowledgments

Neuroscience

Biol Psychiatry

Neurosci Biobehav Rev

Neurosci Biobehav Rev

Neuron

Physiol Behav

Neuroscience

Pain

Curr Opin Neurobiol

Neurosci Biobehav Rev

Biol Psychiatry

Neuroscience

Medial prefrontal cortex determines how stressor controllability affects behavior and dorsal raphe nucleus

Nat Neurosci

Previous experience with behavioral control over stress blocks the behavioral and dorsal raphe nucleus activating effects of later uncontrollable stress: role of the ventral medial prefrontal cortex

J Neurosci

Context and behavioral processes in extinction

Learn Mem

Psychobiological mechanisms of resilience and vulnerability: implications for successful adaptation to extreme stress

Am J Psychiatry

Activity in prelimbic cortex is necessary for the expression of learned, but not innate, fears

J Neurosci

Role of the amygdala in fear extinction measured with potentiated startle

Ann N Y Acad Sci

Relationship of quality of life and perceived control with posttraumatic stress disorder symptoms 3 to 6 months after myocardial infarction

J Cardiopulm Rehabil

Temporary inactivation of the bed nucleus of the stria terminalis but not of the amygdala blocks freezing induced by trimethylthiazoline, a component of fox feces

J Neurosci

Psychosocial treatment of posttraumatic stress disorder

J Clin Psychiatry

Behavioural neuroscience
Controllable versus uncontrollable stressors bi-directionally modulate conditioned but not innate fear