Opioid Receptors Regulate the Extinction of Pavlovian Fear Conditioning.

McNally, Gavan P.; Westbrook, R. Frederick

doi:10.1037/0735-7044.117.6.1292

Cited by 89 publications

(110 citation statements)

References 38 publications

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“…In particular, opioids modulate learning that occurs when there is no shock involved, such as extinction. In fact, earlier work suggested that extinction of active avoidance is impaired by opiate antagonists 213,214 (but see Vigorito and Ayres 215 ) and facilitated by certain opioids 213,214 Consistent with these older findings, McNally and co-workers 216 have found that systemic administration of naloxone before extinction training profoundly retards the development of extinction of freezing to a tone both within and between extinction training sessions. The effect is mediated by central, not peripheral, opioid receptors and is not a consolidation or expression effect because naloxone administration immediately after extinction training or before test has no effect.…”

Section: Neurotransmitter Systemsmentioning

confidence: 69%

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: 69%

Mechanisms of fear extinction

2006

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“…Thus, blocking endogenous μ-opioid neurotransmission enhances the acquisition of conditioned fear (43) and impairs the acquisition of extinction or learned safety (44)(45)(46). The implication of these findings is that μ-opioids are involved in reducing conditioned fear responses and enhancing fear extinction or learned safety.…”

Section: Discussionmentioning

confidence: 95%

Attachment figures activate a safety signal-related neural region and reduce pain experience

Eisenberger

Master

Inagaki

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

432

355

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Although it has long been hypothesized that attachment figures provide individuals with a sense of safety and security, the neural mechanisms underlying attachment-induced safety have not been explored. Here, we investigated whether an attachment figure acts as a safety signal by exploring whether viewing an attachment figure during a threatening experience (physical pain) led to increased activity in a neural region associated with safety signaling, the ventromedial prefrontal cortex (VMPFC), and corresponding reductions in pain. Female participants in long-term romantic relationships were scanned as they received painful stimuli while viewing pictures of their partner and control images (stranger, object). Consistent with the idea that the attachment figure may signal safety, results revealed that viewing partner pictures while receiving painful stimulation led to reductions in self-reported pain ratings, reductions in pain-related neural activity (dorsal anterior cingulate cortex, anterior insula), and increased activity in the VMPFC. Moreover, greater VMPFC activity in response to partner pictures was associated with longer relationship lengths and greater perceived partner support, further highlighting a role for the VMPFC in responding to the safety value of the partner. Last, greater VMPFC activity while viewing partner pictures was associated with reduced pain ratings and reduced pain-related neural activity. An implication of these findings is that, in the same way that stimuli that historically have threatened survival (e.g., snakes, spiders) are considered to be prepared fear stimuli, attachment figures, who have historically benefited survival, may serve as prepared safety stimuli, reducing threat-or distress-related responding in their presence.functional MRI | neuroimaging | close relationship | distress ". . .for a person to know that an attachment figure is available and responsive gives him a strong and pervasive feeling of security. . ." -John Bowlby, 1988 (1) O ne of the central tenets of attachment theory is that the attachment bond-first formed between caregiver and childprovides a sense of safety and security for the child, who is not yet capable of providing or fending for him/herself (2). As suggested by Bowlby (1) above, knowing that an attachment figure is present may serve as a kind of safety signal, letting the individual know that he/she is safe and will be taken care of. Indeed, the presence versus absence of an attachment figure is known to produce quite distinct behavioral profiles in the same child-with courage and exploration seen in the caregiver's presence and timidity and fear observed in the caregiver's absence (2). Although the purpose of this attachment bond is most obvious during childhood, attachment bonds, such as those between adult romantic relationship partners, persist throughout the life cycle and may be beneficial during times of threat or danger (3).Although it makes sense that an attachment figure provides a "pervasive feeling of security," how attachment-induce...

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“…In a Pavlovian fear conditioning paradigm, fear conditioning increases the transcriptional activity of opioidcontaining neurons in the amygdala (Petrovich et al, 2000). Acute administration of opioid antagonists facilitates the acquisition (Fanselow and Bolles, 1979;Young and Fanselow, 1992) and prevents the extinction (McNally and Westbrook, 2003) of fear conditioning.…”

Section: Introductionmentioning

confidence: 99%

Chronic Morphine Selectively Impairs Cued Fear Extinction in Rats: Implications for Anxiety Disorders Associated with Opiate Use

et al. 2007

Neuropsychopharmacol

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Previous studies have shown that opioid transmission plays an important role in learning and memory. However, little is known about the course of opiate-associated learning and memory deficits after cessation of chronic opiate use in a behavioral animal model. In the present study, we examined the effects of chronic morphine on fear extinction, an important preclinical model for behavior therapy of human anxiety disorders. Rats were administrated subcutaneously morphine hydrochloride or saline twice per day for continuous 10 days. Rats received a cued or contextual fear conditioning session 7 days after the last morphine injection. During subsequent days, rats received four cued or contextual extinction sessions (one session per day). Percent freezing was assessed during all phases of training. Chronic morphine did not affect the acquisition of cued fear response or the initial encoding of extinction memory within each session, but produced an impairment in the between-session extinction. However, the same morphine treatment schedule did not affect the acquisition or extinction of contextual fear response. These results suggest that the effects of chronic morphine on memory for fear extinction are complex. Chronic morphine selectively impairs extinction of cued fear response. This deficit in fear extinction may be one of those critical components that contribute to the high prevalence of anxiety disorders in opiate addicts.

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Opioid Receptors Regulate the Extinction of Pavlovian Fear Conditioning.

Cited by 89 publications

References 38 publications

Mechanisms of fear extinction

Mechanisms of fear extinction

Attachment figures activate a safety signal-related neural region and reduce pain experience

Chronic Morphine Selectively Impairs Cued Fear Extinction in Rats: Implications for Anxiety Disorders Associated with Opiate Use

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