Profile of cortical N-methyl-D-aspartate receptor subunit expression associates with inherent motor impulsivity in rats

Davis-Reyes, Brionna D.; Campbell, Veronica M.; Land, Michelle A.; Chapman, Holly; Stafford, Susan; Anastasio, Noelle C.

doi:10.1016/j.bcp.2019.07.007

Cited by 10 publications

(15 citation statements)

References 89 publications

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“…3a , Supplementary Table 10 ), as previously shown in rats 22 , 23 . This model is further supported by the finding that the GluN2B-subunit, specifically, of NMDARs is over-expressed in the PFC of high-impulsive rats 24 . When assessing the anti-impulsive potential of G i - and G q -modulation in ACC L5-PCs in this pharmacological challenge of systemic GluN2B-antagonism, the same pattern emerged as seen with the previous parametric challenges (Fig.…”

Section: Resultsmentioning

confidence: 71%

Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

et al. 2021

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Pathological impulsivity is a debilitating symptom of multiple psychiatric diseases with few effective treatment options. To identify druggable receptors with anti-impulsive action we developed a systematic target discovery approach combining behavioural chemogenetics and gene expression analysis. Spatially restricted inhibition of three subdivisions of the prefrontal cortex of mice revealed that the anterior cingulate cortex (ACC) regulates premature responding, a form of motor impulsivity. Probing three G-protein cascades with designer receptors, we found that the activation of Gi-signalling in layer-5 pyramidal cells (L5-PCs) of the ACC strongly, reproducibly, and selectively decreased challenge-induced impulsivity. Differential gene expression analysis across murine ACC cell-types and 402 GPCRs revealed that - among Gi-coupled receptor-encoding genes - Grm2 is the most selectively expressed in L5-PCs while alternative targets were scarce. Validating our approach, we confirmed that mGluR2 activation reduced premature responding. These results suggest Gi-coupled receptors in ACC L5-PCs as therapeutic targets for impulse control disorders.

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Section: Resultsmentioning

confidence: 71%

Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

et al. 2021

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“…Further implicating PFC glutamatergic dysfunction in impulse control, an altered subunit composition of NMDA receptors was recently identified in trait impulsive rats. Rats deemed highimpulsive on a simple serial reaction time task, showed low expression of GluN1 and GluN2A but increased expression of GluN2B and phosphorylated GluN2B compared with low-impulsive rats (Davis-Reyes et al, 2019). Such findings reinforce translational interest in the GluN2B subunit as a target to treat impulsive and compulsive disorders (Higgins et al, 2016).…”

Section: Glutamatementioning

confidence: 55%

Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective

Jones

Zühlsdorff

Dalley

2021

Journal of Neurochemistry

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Drug compulsion manifests in some but not all individuals and implicates multifaceted processes including failures in top‐down cognitive control as drivers for the hazardous pursuit of drug use in some individuals. As a closely related construct, impulsivity encompasses rash or risky behaviour without foresight and underlies most forms of drug taking behaviour, including drug use during adverse emotional states (i.e., negative urgency). While impulsive behavioural dimensions emerge from drug‐induced brain plasticity, burgeoning evidence suggests that impulsivity also predates the emergence of compulsive drug use. Although the neural substrates underlying the apparently causal relationship between trait impulsivity and drug compulsion are poorly understood, significant advances have come from the interrogation of defined limbic cortico‐striatal circuits involved in motivated behaviour and response inhibition, together with chemical neuromodulatory influences from the ascending neurotransmitter systems. We review what is presently known about the neurochemical mediation of impulsivity, in its various forms, and ask whether commonalities exist in the neurochemistry of compulsive drug‐motivated behaviours that might explain individual risk for addiction. image

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“…One explanation for the diversity of the definitions is the complexity and heterogeneity of impulsivity as a concept. 14 These definitions provide different perspectives regarding the conceptualization of impulsivity in different fields. For example, in the neuroimaging science field, it seems that impulsivity is viewed as a characteristic of making decisions about single discrete behaviors.…”

Section: What This Article Addsmentioning

confidence: 99%

“…Various disciplines introduced different definitions for the concept (Table). One explanation for the diversity of the definitions is the complexity and heterogeneity of impulsivity as a concept 14. These definitions provide different perspectives regarding the conceptualization of impulsivity in different fields.…”

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confidence: 99%

A Review of the Concept of Impulsivity

Al‐Hammouri

Rababah

Shawler³

2021

Advances in Nursing Science

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Impulsivity is a central concept for many psychological models and interventions. Despite extensive research, the concept of impulsivity lacks clarity due to the diversity of definitions provided. The aims of this study were to conduct a concept analysis of impulsivity to provide a clear and workable definition of impulsivity for future nursing research. This study used Rodgers' evolutionary concept analysis approach to analyze 37 articles from various disciplines. Our analysis offers promising direction in refining the concept. The findings can drive future research and enhance nurse researchers' ability to attend and explore health-related issues associated with the concept.

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Profile of cortical N-methyl-D-aspartate receptor subunit expression associates with inherent motor impulsivity in rats

Cited by 10 publications

References 89 publications

Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

Control of impulsivity by Gi-protein signalling in layer-5 pyramidal neurons of the anterior cingulate cortex

Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective

A Review of the Concept of Impulsivity

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