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α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression

Research output: Contribution to Journal/Magazine › Journal article › peer-review

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α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression. / Hawkes, Cheryl A; Heath, Christopher J; Sharp, Matthew M et al.
In: Acta Neuropathologica Communications, Vol. 10, No. 1, 127, 31.08.2022.

Research output: Contribution to Journal/Magazine › Journal article › peer-review

Harvard

Hawkes, CA, Heath, CJ, Sharp, MM, Górecki, DC & Carare, RO 2022, 'α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression', Acta Neuropathologica Communications, vol. 10, no. 1, 127. https://doi.org/10.1186/s40478-022-01434-4

APA

Hawkes, C. A., Heath, C. J., Sharp, M. M., Górecki, D. C., & Carare, R. O. (2022). α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression. Acta Neuropathologica Communications, 10(1), Article 127. https://doi.org/10.1186/s40478-022-01434-4

Vancouver

Hawkes CA, Heath CJ, Sharp MM, Górecki DC, Carare RO. α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression. Acta Neuropathologica Communications. 2022 Aug 31;10(1):127. doi: 10.1186/s40478-022-01434-4

Author

Hawkes, Cheryl A ; Heath, Christopher J ; Sharp, Matthew M et al. / α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression. In: Acta Neuropathologica Communications. 2022 ; Vol. 10, No. 1.

Bibtex

@article{e3394ad795f34a74aef1e0b8ed7ef041,
title = "α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression",
abstract = "α-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems. [Abstract copyright: {\textcopyright} 2022. The Author(s).]",
keywords = "Humans, Motivation, Mice, Knockout, Brain - metabolism, Endocannabinoid, α-Dystrobrevin, Animals, Dysbindin - metabolism, Dystrophin-Associated Proteins, RNA, Messenger - metabolism, Reward, Mice, Male, Receptors, Cannabinoid - metabolism, Appetitive motivation, Brain, Dopamine - metabolism",
author = "Hawkes, {Cheryl A} and Heath, {Christopher J} and Sharp, {Matthew M} and G{\'o}recki, {Dariusz C} and Carare, {Roxana O}",
year = "2022",
month = aug,
day = "31",
doi = "10.1186/s40478-022-01434-4",
language = "English",
volume = "10",
journal = "Acta Neuropathologica Communications",
issn = "2051-5960",
publisher = "BMC",
number = "1",

}

RIS

TY - JOUR

T1 - α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression

AU - Hawkes, Cheryl A

AU - Heath, Christopher J

AU - Sharp, Matthew M

AU - Górecki, Dariusz C

AU - Carare, Roxana O

PY - 2022/8/31

Y1 - 2022/8/31

N2 - α-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems. [Abstract copyright: © 2022. The Author(s).]

AB - α-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems. [Abstract copyright: © 2022. The Author(s).]

KW - Humans

KW - Motivation

KW - Mice, Knockout

KW - Brain - metabolism

KW - Endocannabinoid

KW - α-Dystrobrevin

KW - Animals

KW - Dysbindin - metabolism

KW - Dystrophin-Associated Proteins

KW - RNA, Messenger - metabolism

KW - Reward

KW - Mice

KW - Male

KW - Receptors, Cannabinoid - metabolism

KW - Appetitive motivation

KW - Brain

KW - Dopamine - metabolism

U2 - 10.1186/s40478-022-01434-4

DO - 10.1186/s40478-022-01434-4

M3 - Journal article

C2 - 36045406

VL - 10

JO - Acta Neuropathologica Communications

JF - Acta Neuropathologica Communications

SN - 2051-5960

IS - 1

M1 - 127

ER -