SKF83959, an agonist of phosphatidylinositol-linked dopamine receptors, prevents renewal of extinguished conditioned fear and facilitates extinction

Chen, Fu-Feng; Wang, Canming; Chen, Hongsheng; Ji, Wang; Han, Qian-Qian; Cao, Yu; Shen, Tiantian; Yang, Yuan-Jian; Hu, Zhuang-Li; Wang, Fang; Chen, Jianguo; Wu, Peng

doi:10.1016/j.brainres.2020.147136

Cited by 6 publications

(7 citation statements)

References 54 publications

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“…However, no significant difference was found between the SKF83959-treated group and the epilepsy group (Figure G–I). Other research studies also did not observe the anxiolytic effect of SKF83959. , Thus, we concluded that SKF83959 did not change the anxiety status of epileptic mice.…”

Section: Resultssupporting

confidence: 43%

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SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

Guo

Gao

Jia

et al. 2022

ACS Chem. Neurosci.

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Memory impairment and emotional disorder are two common clinical comorbidities in patients with epilepsy. It is imperative to develop a novel therapeutic agent or a strategy. 6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is a dopamine-1 receptor agonist and sigma-1 receptor allosteric modulator, which displays the neuron-protective and anti-neuroinflammation activity. We examined the effect of SKF83959 on the memory impairment and emotional disorder in the latent period of epilepsy using the mice post-status epilepticus model. We found that SKF83959 ameliorated memory impairment and depressive-like mood, alleviated the neuron damage and the formation of gliosis in hippocampus, suppressed the rise of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, and induced nitric oxide synthase in the latent period of epilepsy. Additionally, SKF83959 significantly inhibited the activity of calcineurin and glycogen synthase kinase-3β. All of these protective actions were reversed by BD1047 (a sigma-1 receptor antagonist). In addition, the intra-hippocampus injection of ketoconazole (a dehydroepiandrosterone synthesis inhibitor) also reversed the protective activity of SKF83959. Thus, we concluded that SKF83959 ameliorated the memory impairment and depressive-like mood in epilepsy via allosterically activating the sigma-1 receptor and subsequently inhibiting the calcineurin/glycogen synthase kinase-3β pathway.

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Section: Resultssupporting

confidence: 43%

“…Other research studies also did not observe the anxiolytic effect of SKF83959. 17,18 Thus, we concluded that SKF83959 did not change the anxiety status of epileptic mice.…”

Section: ■ Results and Discussionmentioning

confidence: 76%

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

Guo

Gao

Jia

et al. 2022

ACS Chem. Neurosci.

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“…However, Drd1 knockout mice displayed impaired extinction training and extinction recall in some cases (Abraham et al, 2016a; El‐Ghundi et al, 2001), but not in others (Ortiz et al, 2010; Table S7). Additionally, D 1 ‐like receptor agonists may have different effects on extinction training and recall depending on baseline DA levels and may disrupt renewal and reinstatement (Table 3; Chen, Wang, et al, 2020; Rey et al, 2014). Drd5 knockout mice did not show deficits in fear conditioning (Holmes et al, 2001; Table S7).…”

Section: Resultsmentioning

confidence: 99%

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

Hamati,

Ahrens,

Shvetz

et al. 2023

Eur J of Neuroscience

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Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gathered the vast evidence of the role of dopamine in the simplest forms of aversive learning: classical fear conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic and optogenetic approaches now provide causal evidence for dopamine's role in these learning processes. Dopamine neurons encode conditioned stimuli during fear conditioning and extinction and convey the signal via activation of D1–4 receptor sites particularly in the amygdala, prefrontal cortex and striatum. The coordinated activation of dopamine receptors allows for the continuous formation, consolidation, retrieval and updating of fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of classical fear conditioning and extinction and contributes in a way that is comparable to its role in encoding reward.

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“…D 1 -like receptor agonists may have different effects on extinction recall depending on baseline dopamine levels (Rey et al, 2014; Table 3). These agonists can also improve extinction and extinction recall, but may disrupt renewal and reinstatement (Chen et al, 2020). In sum, it is likely that both D 1 and D 5 receptors are involved in fear acquisition and consolidation, but they may not play a role in the fear recall.…”

Section: Stimulation or Inhibition Of Da In The Striatummentioning

confidence: 99%

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

Hamati

Ahrens

Holahan

et al. 2023

Preprint

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Dopamine, a catecholamine neurotransmitter, has historically been associated with the encoding of reward, whereas its role in aversion has received less attention. Here, we systematically gather the vast evidence for a role of dopamine in the simplest form of aversive learning: passive aversive conditioning and extinction. In the past, crude methods were used to augment or inhibit dopamine in order to study its relationship with fear conditioning and extinction. More advanced techniques such as conditional genetic, chemogenic, and optogenetic approaches now provide causal evidence for dopamine’s role in these learning processes. Dopamine neurons encode fear and extinction-related information and convey the signal via activation of D1, D2, D3, and D4 receptor sites particularly in the amygdala, prefrontal cortex, and striatum in order to continuously form, consolidate, retrieve, and update fear and extinction memory in a dynamic and reciprocal manner. Based on the reviewed literature, we conclude that dopamine is crucial for the encoding of passive aversive conditioning and contributes in a way that is comparable to its role in encoding reward.

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SKF83959, an agonist of phosphatidylinositol-linked dopamine receptors, prevents renewal of extinguished conditioned fear and facilitates extinction

Cited by 6 publications

References 54 publications

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

SKF83959 Attenuates Memory Impairment and Depressive-like Behavior during the Latent Period of Epilepsy via Allosteric Activation of the Sigma-1 Receptor

65 years of research on dopamine's role in classical fear conditioning and extinction: A systematic review

50 Years of Research on Dopamine’s Role in Passive Aversive Conditioning and Extinction: A Systematic Review

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