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PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis

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Harvard

Jensen, KL, Sørensen, G, Dencker, D, Owens, WA, Rahbek-Clemmensen, T, Brett Lever, M, Runegaard, AH, Riis Christensen, N, Weikop, P, Wörtwein, G, Fink-Jensen, A, Madsen, KL, Daws, L, Gether, U & Rickhag, M 2018, 'PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis', eNeuro, bind 5, nr. 3. https://doi.org/10.1523/ENEURO.0422-17.2018

APA

Jensen, K. L., Sørensen, G., Dencker, D., Owens, W. A., Rahbek-Clemmensen, T., Brett Lever, M., Runegaard, A. H., Riis Christensen, N., Weikop, P., Wörtwein, G., Fink-Jensen, A., Madsen, K. L., Daws, L., Gether, U., & Rickhag, M. (2018). PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis. eNeuro, 5(3). https://doi.org/10.1523/ENEURO.0422-17.2018

CBE

Jensen KL, Sørensen G, Dencker D, Owens WA, Rahbek-Clemmensen T, Brett Lever M, Runegaard AH, Riis Christensen N, Weikop P, Wörtwein G, Fink-Jensen A, Madsen KL, Daws L, Gether U, Rickhag M. 2018. PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis. eNeuro. 5(3). https://doi.org/10.1523/ENEURO.0422-17.2018

MLA

Vancouver

Author

Jensen, Kathrine Louise ; Sørensen, Gunnar ; Dencker, Ditte ; Owens, William Anthony ; Rahbek-Clemmensen, Troels ; Brett Lever, Michael ; Runegaard, Annika H ; Riis Christensen, Nikolaj ; Weikop, Pia ; Wörtwein, Gitta ; Fink-Jensen, Anders ; Madsen, Kenneth L ; Daws, Lynette ; Gether, Ulrik ; Rickhag, Mattias. / PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis. I: eNeuro. 2018 ; Bind 5, Nr. 3.

Bibtex

@article{52c12c5c4f7d41b88073db0be9293f1a,
title = "PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis",
abstract = "Protein interacting with C-kinase 1 (PICK1) is a widely expressed scaffold protein known to interact via its PSD-95/discs-large/ZO-1 (PDZ)-domain with several membrane proteins including the dopamine (DA) transporter (DAT), the primary target for cocaine's reinforcing actions. Here, we establish the importance of PICK1 for behavioral effects observed after both acute and repeated administration of cocaine. In PICK1 knock-out (KO) mice, the acute locomotor response to a single injection of cocaine was markedly attenuated. Moreover, in support of a role for PICK1 in neuroadaptive changes induced by cocaine, we observed diminished cocaine intake in a self-administration paradigm. Reduced behavioral effects of cocaine were not associated with decreased striatal DAT distribution and most likely not caused by the ∼30% reduction in synaptosomal DA uptake observed in PICK1 KO mice. The PICK1 KO mice demonstrated preserved behavioral responses to DA receptor agonists supporting intact downstream DA receptor signaling. Unexpectedly, we found a prominent increase in striatal DA content and levels of striatal tyrosine hydroxylase (TH) in PICK1 KO mice. Chronoamperometric recordings showed enhanced DA release in PICK1 KO mice, consistent with increased striatal DA pools. Viral-mediated knock-down (KD) of PICK1 in cultured dopaminergic neurons increased TH expression, supporting a direct cellular effect of PICK1. In summary, in addition to demonstrating a key role of PICK1 in mediating behavioral effects of cocaine, our data reveal a so far unappreciated role of PICK1 in DA homeostasis that possibly involves negative regulation of striatal TH levels.",
keywords = "Animals, Carrier Proteins/genetics, Cocaine/administration & dosage, Corpus Striatum/drug effects, Dopamine/metabolism, Dopamine Plasma Membrane Transport Proteins/metabolism, Dopaminergic Neurons/drug effects, Homeostasis/drug effects, Locomotion/drug effects, Male, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins/genetics, Reinforcement (Psychology), Signal Transduction/drug effects, Tyrosine 3-Monooxygenase/metabolism",
author = "Jensen, {Kathrine Louise} and Gunnar S{\o}rensen and Ditte Dencker and Owens, {William Anthony} and Troels Rahbek-Clemmensen and {Brett Lever}, Michael and Runegaard, {Annika H} and {Riis Christensen}, Nikolaj and Pia Weikop and Gitta W{\"o}rtwein and Anders Fink-Jensen and Madsen, {Kenneth L} and Lynette Daws and Ulrik Gether and Mattias Rickhag",
year = "2018",
month = jun,
day = "11",
doi = "10.1523/ENEURO.0422-17.2018",
language = "English",
volume = "5",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society for Neuroscience",
number = "3",

}

RIS

TY - JOUR

T1 - PICK1-Deficient Mice Exhibit Impaired Response to Cocaine and Dysregulated Dopamine Homeostasis

AU - Jensen, Kathrine Louise

AU - Sørensen, Gunnar

AU - Dencker, Ditte

AU - Owens, William Anthony

AU - Rahbek-Clemmensen, Troels

AU - Brett Lever, Michael

AU - Runegaard, Annika H

AU - Riis Christensen, Nikolaj

AU - Weikop, Pia

AU - Wörtwein, Gitta

AU - Fink-Jensen, Anders

AU - Madsen, Kenneth L

AU - Daws, Lynette

AU - Gether, Ulrik

AU - Rickhag, Mattias

PY - 2018/6/11

Y1 - 2018/6/11

N2 - Protein interacting with C-kinase 1 (PICK1) is a widely expressed scaffold protein known to interact via its PSD-95/discs-large/ZO-1 (PDZ)-domain with several membrane proteins including the dopamine (DA) transporter (DAT), the primary target for cocaine's reinforcing actions. Here, we establish the importance of PICK1 for behavioral effects observed after both acute and repeated administration of cocaine. In PICK1 knock-out (KO) mice, the acute locomotor response to a single injection of cocaine was markedly attenuated. Moreover, in support of a role for PICK1 in neuroadaptive changes induced by cocaine, we observed diminished cocaine intake in a self-administration paradigm. Reduced behavioral effects of cocaine were not associated with decreased striatal DAT distribution and most likely not caused by the ∼30% reduction in synaptosomal DA uptake observed in PICK1 KO mice. The PICK1 KO mice demonstrated preserved behavioral responses to DA receptor agonists supporting intact downstream DA receptor signaling. Unexpectedly, we found a prominent increase in striatal DA content and levels of striatal tyrosine hydroxylase (TH) in PICK1 KO mice. Chronoamperometric recordings showed enhanced DA release in PICK1 KO mice, consistent with increased striatal DA pools. Viral-mediated knock-down (KD) of PICK1 in cultured dopaminergic neurons increased TH expression, supporting a direct cellular effect of PICK1. In summary, in addition to demonstrating a key role of PICK1 in mediating behavioral effects of cocaine, our data reveal a so far unappreciated role of PICK1 in DA homeostasis that possibly involves negative regulation of striatal TH levels.

AB - Protein interacting with C-kinase 1 (PICK1) is a widely expressed scaffold protein known to interact via its PSD-95/discs-large/ZO-1 (PDZ)-domain with several membrane proteins including the dopamine (DA) transporter (DAT), the primary target for cocaine's reinforcing actions. Here, we establish the importance of PICK1 for behavioral effects observed after both acute and repeated administration of cocaine. In PICK1 knock-out (KO) mice, the acute locomotor response to a single injection of cocaine was markedly attenuated. Moreover, in support of a role for PICK1 in neuroadaptive changes induced by cocaine, we observed diminished cocaine intake in a self-administration paradigm. Reduced behavioral effects of cocaine were not associated with decreased striatal DAT distribution and most likely not caused by the ∼30% reduction in synaptosomal DA uptake observed in PICK1 KO mice. The PICK1 KO mice demonstrated preserved behavioral responses to DA receptor agonists supporting intact downstream DA receptor signaling. Unexpectedly, we found a prominent increase in striatal DA content and levels of striatal tyrosine hydroxylase (TH) in PICK1 KO mice. Chronoamperometric recordings showed enhanced DA release in PICK1 KO mice, consistent with increased striatal DA pools. Viral-mediated knock-down (KD) of PICK1 in cultured dopaminergic neurons increased TH expression, supporting a direct cellular effect of PICK1. In summary, in addition to demonstrating a key role of PICK1 in mediating behavioral effects of cocaine, our data reveal a so far unappreciated role of PICK1 in DA homeostasis that possibly involves negative regulation of striatal TH levels.

KW - Animals

KW - Carrier Proteins/genetics

KW - Cocaine/administration & dosage

KW - Corpus Striatum/drug effects

KW - Dopamine/metabolism

KW - Dopamine Plasma Membrane Transport Proteins/metabolism

KW - Dopaminergic Neurons/drug effects

KW - Homeostasis/drug effects

KW - Locomotion/drug effects

KW - Male

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Nuclear Proteins/genetics

KW - Reinforcement (Psychology)

KW - Signal Transduction/drug effects

KW - Tyrosine 3-Monooxygenase/metabolism

U2 - 10.1523/ENEURO.0422-17.2018

DO - 10.1523/ENEURO.0422-17.2018

M3 - Journal article

C2 - 29911172

VL - 5

JO - eNeuro

JF - eNeuro

SN - 2373-2822

IS - 3

ER -

ID: 56440570