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阻断伏隔核中的多巴胺活动会损害条件性恐惧学习的消退。

Blockade of dopamine activity in the nucleus accumbens impairs learning extinction of conditioned fear.

机构信息

School of Psychology, University of New South Wales, Sydney, New South Wales 2052, Australia.

出版信息

Learn Mem. 2010 Feb 13;17(2):71-5. doi: 10.1101/lm.1668310. Print 2010 Feb.


DOI:10.1101/lm.1668310
PMID:20154351
Abstract

Three experiments used rats to investigate the role of dopamine activity in learning to inhibit conditioned fear responses (freezing) in extinction. In Experiment 1, rats systemically injected with the D2 dopamine antagonist, haloperidol, froze more across multiple extinction sessions and on a drug-free retention test than control rats. In Experiment 2, rats extinguished under an intracerebroventricular (ICV) infusion of haloperidol suppressed fear responses across extinction but froze more on a subsequent drug-free retention test than control rats. In Experiment 3, rats extinguished under an infusion of haloperidol in the nucleus accumbens were impaired in suppressing fear responses across extinction and froze more on subsequent drug-free retention test than control rats. These results show that learning to inhibit fear responses in extinction requires dopamine activity in the nucleus accumbens. They were interpreted to mean that dopaminergic activity in the nucleus accumbens regulates the prediction error required for learning to inhibit fear responses in extinction.

摘要

三项实验使用大鼠来探究多巴胺活动在学习抑制条件性恐惧反应(冻结)的消退中的作用。在实验 1 中,与对照组大鼠相比,系统注射 D2 多巴胺拮抗剂氟哌啶醇的大鼠在多次消退过程中以及在无药物保留测试中冻结的次数更多。在实验 2 中,在脑室内(ICV)输注氟哌啶醇的大鼠在消退过程中抑制了恐惧反应,但与对照组大鼠相比,在随后的无药物保留测试中冻结的次数更多。在实验 3 中,在伏隔核中输注氟哌啶醇的大鼠在消退过程中抑制恐惧反应的能力受损,并且在随后的无药物保留测试中冻结的次数比对照组大鼠更多。这些结果表明,在消退中学习抑制恐惧反应需要伏隔核中的多巴胺活动。这些结果被解释为意味着伏隔核中的多巴胺活性调节了在消退中学习抑制恐惧反应所需的预测误差。

相似文献

[1]
Blockade of dopamine activity in the nucleus accumbens impairs learning extinction of conditioned fear.

Learn Mem. 2010-2-13

[2]
Role of the basolateral amygdala in the reinstatement and extinction of fear responses to a previously extinguished conditioned stimulus.

Learn Mem. 2010-2-13

[3]
Systemic or intra-amygdala infusion of the benzodiazepine, midazolam, impairs learning, but facilitates re-learning to inhibit fear responses in extinction.

Learn Mem. 2010-3-26

[4]
US habituation, like CS extinction, produces a decrement in conditioned fear responding that is NMDA dependent and subject to renewal and reinstatement.

Neurobiol Learn Mem. 2010-1-13

[5]
Effects of REM deprivation and an NMDA agonist on the extinction of conditioned fear.

Physiol Behav. 2008-1-28

[6]
Distinct contributions of the basolateral amygdala and the medial prefrontal cortex to learning and relearning extinction of context conditioned fear.

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[7]
The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response.

Neurobiol Learn Mem. 2009-11

[8]
Impairment of contextual conditioned fear extinction after microinjection of alpha-1-adrenergic blocker prazosin into the medial prefrontal cortex.

Behav Brain Res. 2010-3-19

[9]
Opioid receptors regulate the extinction of Pavlovian fear conditioning.

Behav Neurosci. 2003-12

[10]
The effect of the NMDA receptor antagonist MK-801 on the acquisition and extinction of learned fear in the developing rat.

Learn Mem. 2007-9-25

引用本文的文献

[1]
Dopamine induces fear extinction by activating the reward-responding amygdala neurons.

Proc Natl Acad Sci U S A. 2025-5-6

[2]
Dynamic representation of appetitive and aversive stimuli in nucleus accumbens shell D1- and D2-medium spiny neurons.

Nat Commun. 2025-1-2

[3]
Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction.

Mol Psychiatry. 2025-6

[4]
Sex Differences in Contextual Extinction Learning After Single Binge-Like EtOH Exposure in Adolescent C57BL/6J Mice.

bioRxiv. 2024-10-26

[5]
Pharmacological manipulations of the dorsomedial and dorsolateral striatum during fear extinction reveal opposing roles in fear renewal.

Neurobiol Learn Mem. 2024-7

[6]
Effects of chronic haloperidol treatment on the expression of fear memory and fear memory extinction in the cued fear-conditioned rats.

Neuropsychopharmacol Rep. 2024-3

[7]
Role of nucleus accumbens D1-type medium spiny neurons in the expression and extinction of sign-tracking.

Behav Brain Res. 2024-2-29

[8]
The Basolateral Amygdala: The Core of a Network for Threat Conditioning, Extinction, and Second-Order Threat Conditioning.

Biology (Basel). 2023-9-22

[9]
Involvement of D2-like dopaminergic receptors in contextual fear conditioning in female rats: influence of estrous cycle.

Front Behav Neurosci. 2022-11-28

[10]
Rewarded Extinction Increases Amygdalar Connectivity and Stabilizes Long-Term Memory Traces in the vmPFC.

J Neurosci. 2022-7-20

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