Opioid receptors in the midbrain periaqueductal gray regulate prediction errors during Pavlovian fear conditioning.

McNally, Gavan P.; Cole, Sindy

doi:10.1037/0735-7044.120.2.313

Cited by 84 publications

(96 citation statements)

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“…80,210,219 This effect, like the retardation of extinction, is mimicked by infusion of naloxone or the m opioid antagonist CTAP directly into vlPAG. 80 The second additional phenomenon examined by McNally and co-workers is overexpectation, in which two CSs, C and D, are paired with the US separately in one phase of training, then are paired with the US in compound in a second phase (lower panel of Figure 4). Despite 100% reinforcement of C and D throughout the experiment, both CSs are observed to elicit less fear at the conclusion of phase 2 than they did at the conclusion of phase 1.…”

Section: Neurotransmitter Systemsmentioning

confidence: 98%

“…Brain structures Several brain structures have been implicated in fear extinction and fear inhibition more generally, including sensory cortex, [74][75][76][77][78] periaqueductal gray [79][80][81] (see below), inferior colliculus, 82 lateral septum, [83][84][85][86] bed nucleus of the stria terminalis, 87 and ventral 88 and dorsal striatum. 89 In this section, we will focus on those for which there is the most information available: the amygdala, hippocampus and prefrontal cortex.…”

Section: Neural Mechanismsmentioning

confidence: 99%

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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: Neurotransmitter Systemsmentioning

confidence: 98%

Section: Neural Mechanismsmentioning

confidence: 99%

Mechanisms of fear extinction

2006

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“…Previous studies have shown that systemic administrations of naloxone prevent the blocking of conditioned fear (Fanselow and Bolles 1979;Matzel et al 1988;McNally et al 2004a;McNally and Cole 2006). However, these studies have focused on multi-trial blocking.…”

Section: Experiments 3: Effects Of Naloxone On One-trial Blocking Of Fmentioning

confidence: 97%

“…A CS which is a better predictor of the outcome will command more attention and consequently be better learned about than a CS which is a poorer predictor and which is consequently ignored. McNally and Cole (2006) demonstrated that vlPAG µ-opioid receptors contribute to predictive fear learning. However, the design of those experiments did not permit examination of whether this µ-opioid receptor contribution to predictive fear learning was direct and achieved via alterations in US processing or indirect and achieved via alterations in CS processing.…”

mentioning

confidence: 99%

“…In contrast, the neural mechanisms of predictive fear learning remain poorly understood. Using a within-subject blocking design, McNally and Cole (2006) demonstrated that µ-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG) mediate predictive error during fear learning. Rats were conditioned to fear CSA via pairings with footshock.…”

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confidence: 99%

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Opioid receptors mediate direct predictive fear learning: Evidence from one-trial blocking

Cole¹,

McNally²

2007

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Pavlovian fear learning depends on predictive error, so that fear learning occurs when the actual outcome of a conditioning trial exceeds the expected outcome. Previous research has shown that opioid receptors, including µ-opioid receptors in the ventrolateral quadrant of the midbrain periaqueductal gray (vlPAG), mediate such predictive fear learning. Four experiments reported here used a within-subject one-trial blocking design to study whether opioid receptors mediate a direct or indirect action of predictive error on Pavlovian association formation. In Stage I, rats were trained to fear conditioned stimulus (CS) A by pairing it with shock. In Stage II, CSA and CSB were co-presented once and co-terminated with shock. Two novel stimuli, CSC and CSD, were also co-presented once and co-terminated with shock in Stage II. The results showed one-trial blocking of fear learning (Experiment 1) as well as one-trial unblocking of fear learning when Stage II training employed a higher intensity footshock than was used in Stage I (Experiment 2). Systemic administrations of the opioid receptor antagonist naloxone (Experiment 3) or intra-vlPAG administrations of the selective µ-opioid receptor antagonist CTAP (Experiment 4) prior to Stage II training prevented one-trial blocking. These results show that opioid receptors mediate the direct actions of predictive error on Pavlovian association formation.Learning about the predictive relations existing between events in the world is central to adaptive behavior. It allows us to use the past to predict the future and to adjust our behavior accordingly. Prediction has been formalized in experimental psychology through error-correcting learning rules (Dickinson 1980;Rescorla 1988). In Pavlovian conditioning these rules state that fear accrues to a conditioned stimulus (CS) which signals an aversive unconditioned stimulus (US) when the actual outcome of the conditioning trial exceeds the predicted outcome, i.e., when there is a positive prediction error. Likewise, fear to a CS will typically be lost when the predicted outcome exceeds the actual outcome, i.e., when there is a negative prediction error. The paradigmatic demonstration of a role for predictive error in learning is "blocking". Kamin (1968Kamin ( , 1969) subjected rats to CSA-shock pairings. In Stage II, rats received a compound stimulus of CSA and CSB paired with shock. A control group received Stage II training but no Stage I training. The control group showed robust fear of CSB. However, for the experimental group learning to CSB failed. Conditioning failed to CSB, despite AB-shock pairings, because predictive error during Stage II was low: Subjects could predict the occurrence of shock from CSA and so learning about CSB was "blocked."The neural mechanisms for the encoding, storage, and retrieval of fear memories are remarkably well understood. Activation of NMDA receptors in the amygdala and recruitment of the signal transduction cascades subsequent to NMDA receptor activation (e.g., Ca 2+ and cyclic AMP-dependent si...

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Neurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD

Bremner

Pearce

2016

Posttraumatic Stress Disorder

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Opioid receptors in the midbrain periaqueductal gray regulate prediction errors during Pavlovian fear conditioning.

Cited by 84 publications

References 44 publications

Mechanisms of fear extinction

Mechanisms of fear extinction

Opioid receptors mediate direct predictive fear learning: Evidence from one-trial blocking

Neurotransmitter, neurohormonal, and neuropeptidal function in stress and PTSD

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