Manuel Mattheisen

αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Standard

αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior. / Easton, Alanna C; Lucchesi, Walter; Lourdusamy, Anbarasu; Lenz, Bernd; Solati, Jalal; Golub, Yulia; Lewczuk, Piotr; Fernandes, Cathy; Desrivieres, Sylvane; Dawirs, Ralph R; Moll, Gunther H; Kornhuber, Johannes; Frank, Josef; Hoffmann, Per; Soyka, Michael; Kiefer, Falk; Schumann, Gunter; Peter Giese, K; Müller, Christian P; Treutlein, Jens; Cichon, Sven; Ridinger, Monika; Mattheisen, Manuel; Herms, Stefan; Wodarz, Norbert; Zill, Peter; Maier, Wolfgang; Mössner, Rainald; Gaebel, Wolfgang; Dahmen, Norbert; Scherbaum, Norbert; Schmäl, Christine; Steffens, Michael; Lucae, Susanne; Ising, Marcus; Müller-Myhsok, Bertram; Nöthen, Markus M; Mann, Karl; Rietschel, Marcella; GESGA Consortium ; Mattheisen, Manuel.

In: Neuropsychopharmacology, Vol. 38, No. 9, 08.2013, p. 1636-47.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Easton, AC, Lucchesi, W, Lourdusamy, A, Lenz, B, Solati, J, Golub, Y, Lewczuk, P, Fernandes, C, Desrivieres, S, Dawirs, RR, Moll, GH, Kornhuber, J, Frank, J, Hoffmann, P, Soyka, M, Kiefer, F, Schumann, G, Peter Giese, K, Müller, CP, Treutlein, J, Cichon, S, Ridinger, M, Mattheisen, M, Herms, S, Wodarz, N, Zill, P, Maier, W, Mössner, R, Gaebel, W, Dahmen, N, Scherbaum, N, Schmäl, C, Steffens, M, Lucae, S, Ising, M, Müller-Myhsok, B, Nöthen, MM, Mann, K, Rietschel, M, GESGA Consortium & Mattheisen, M 2013, 'αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior', Neuropsychopharmacology, vol. 38, no. 9, pp. 1636-47. https://doi.org/10.1038/npp.2013.60

APA

Easton, A. C., Lucchesi, W., Lourdusamy, A., Lenz, B., Solati, J., Golub, Y., Lewczuk, P., Fernandes, C., Desrivieres, S., Dawirs, R. R., Moll, G. H., Kornhuber, J., Frank, J., Hoffmann, P., Soyka, M., Kiefer, F., Schumann, G., Peter Giese, K., Müller, C. P., ... Mattheisen, M. (2013). αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior. Neuropsychopharmacology, 38(9), 1636-47. https://doi.org/10.1038/npp.2013.60

CBE

Easton AC, Lucchesi W, Lourdusamy A, Lenz B, Solati J, Golub Y, Lewczuk P, Fernandes C, Desrivieres S, Dawirs RR, Moll GH, Kornhuber J, Frank J, Hoffmann P, Soyka M, Kiefer F, Schumann G, Peter Giese K, Müller CP, Treutlein J, Cichon S, Ridinger M, Mattheisen M, Herms S, Wodarz N, Zill P, Maier W, Mössner R, Gaebel W, Dahmen N, Scherbaum N, Schmäl C, Steffens M, Lucae S, Ising M, Müller-Myhsok B, Nöthen MM, Mann K, Rietschel M, GESGA Consortium, Mattheisen M. 2013. αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior. Neuropsychopharmacology. 38(9):1636-47. https://doi.org/10.1038/npp.2013.60

MLA

Vancouver

Easton AC, Lucchesi W, Lourdusamy A, Lenz B, Solati J, Golub Y et al. αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior. Neuropsychopharmacology. 2013 Aug;38(9):1636-47. https://doi.org/10.1038/npp.2013.60

Author

Easton, Alanna C ; Lucchesi, Walter ; Lourdusamy, Anbarasu ; Lenz, Bernd ; Solati, Jalal ; Golub, Yulia ; Lewczuk, Piotr ; Fernandes, Cathy ; Desrivieres, Sylvane ; Dawirs, Ralph R ; Moll, Gunther H ; Kornhuber, Johannes ; Frank, Josef ; Hoffmann, Per ; Soyka, Michael ; Kiefer, Falk ; Schumann, Gunter ; Peter Giese, K ; Müller, Christian P ; Treutlein, Jens ; Cichon, Sven ; Ridinger, Monika ; Mattheisen, Manuel ; Herms, Stefan ; Wodarz, Norbert ; Zill, Peter ; Maier, Wolfgang ; Mössner, Rainald ; Gaebel, Wolfgang ; Dahmen, Norbert ; Scherbaum, Norbert ; Schmäl, Christine ; Steffens, Michael ; Lucae, Susanne ; Ising, Marcus ; Müller-Myhsok, Bertram ; Nöthen, Markus M ; Mann, Karl ; Rietschel, Marcella ; GESGA Consortium ; Mattheisen, Manuel. / αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior. In: Neuropsychopharmacology. 2013 ; Vol. 38, No. 9. pp. 1636-47.

Bibtex

@article{898a17ccd7b54b2b969d45d0488e29cb,
title = "αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior",
abstract = "The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKII(T286A) mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKII(T286A) mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKII(T286A) mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.",
keywords = "Alcohol Drinking, Alcoholism, Animals, Behavior, Addictive, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Case-Control Studies, Dopamine, Dose-Response Relationship, Drug, Ethanol, Female, Genetic Predisposition to Disease, Humans, Hypnotics and Sedatives, Male, Mice, Motor Activity, Nucleus Accumbens, Phosphorylation, Polymorphism, Single Nucleotide, Prefrontal Cortex, Serotonin, Ventral Tegmental Area",
author = "Easton, {Alanna C} and Walter Lucchesi and Anbarasu Lourdusamy and Bernd Lenz and Jalal Solati and Yulia Golub and Piotr Lewczuk and Cathy Fernandes and Sylvane Desrivieres and Dawirs, {Ralph R} and Moll, {Gunther H} and Johannes Kornhuber and Josef Frank and Per Hoffmann and Michael Soyka and Falk Kiefer and Gunter Schumann and {Peter Giese}, K and M{\"u}ller, {Christian P} and Jens Treutlein and Sven Cichon and Monika Ridinger and Manuel Mattheisen and Stefan Herms and Norbert Wodarz and Peter Zill and Wolfgang Maier and Rainald M{\"o}ssner and Wolfgang Gaebel and Norbert Dahmen and Norbert Scherbaum and Christine Schm{\"a}l and Michael Steffens and Susanne Lucae and Marcus Ising and Bertram M{\"u}ller-Myhsok and N{\"o}then, {Markus M} and Karl Mann and Marcella Rietschel and {GESGA Consortium} and Manuel Mattheisen",
year = "2013",
month = aug,
doi = "10.1038/npp.2013.60",
language = "English",
volume = "38",
pages = "1636--47",
journal = "Neuropsychopharmacology",
issn = "0893-133X",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - αCaMKII autophosphorylation controls the establishment of alcohol drinking behavior

AU - Easton, Alanna C

AU - Lucchesi, Walter

AU - Lourdusamy, Anbarasu

AU - Lenz, Bernd

AU - Solati, Jalal

AU - Golub, Yulia

AU - Lewczuk, Piotr

AU - Fernandes, Cathy

AU - Desrivieres, Sylvane

AU - Dawirs, Ralph R

AU - Moll, Gunther H

AU - Kornhuber, Johannes

AU - Frank, Josef

AU - Hoffmann, Per

AU - Soyka, Michael

AU - Kiefer, Falk

AU - Schumann, Gunter

AU - Peter Giese, K

AU - Müller, Christian P

AU - Treutlein, Jens

AU - Cichon, Sven

AU - Ridinger, Monika

AU - Mattheisen, Manuel

AU - Herms, Stefan

AU - Wodarz, Norbert

AU - Zill, Peter

AU - Maier, Wolfgang

AU - Mössner, Rainald

AU - Gaebel, Wolfgang

AU - Dahmen, Norbert

AU - Scherbaum, Norbert

AU - Schmäl, Christine

AU - Steffens, Michael

AU - Lucae, Susanne

AU - Ising, Marcus

AU - Müller-Myhsok, Bertram

AU - Nöthen, Markus M

AU - Mann, Karl

AU - Rietschel, Marcella

AU - GESGA Consortium

AU - Mattheisen, Manuel

PY - 2013/8

Y1 - 2013/8

N2 - The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKII(T286A) mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKII(T286A) mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKII(T286A) mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.

AB - The α-Ca(2+)/calmodulin-dependent protein kinase II (αCaMKII) is a crucial enzyme controlling plasticity in the brain. The autophosphorylation of αCaMKII works as a 'molecular memory' for a transient calcium activation, thereby accelerating learning. We investigated the role of αCaMKII autophosphorylation in the establishment of alcohol drinking as an addiction-related behavior in mice. We found that alcohol drinking was initially diminished in αCaMKII autophosphorylation-deficient αCaMKII(T286A) mice, but could be established at wild-type level after repeated withdrawals. The locomotor activating effects of a low-dose alcohol (2 g/kg) were absent in αCaMKII(T286A) mice, whereas the sedating effects of high-dose (3.5 g/kg) were preserved after acute and subchronic administration. The in vivo microdialysis revealed that αCaMKII(T286A) mice showed no dopamine (DA) response in the nucleus accumbens to acute or subchronic alcohol administration, but enhanced serotonin (5-HT) responses in the prefrontal cortex. The attenuated DA response in αCaMKII(T286A) mice was in line with altered c-Fos activation in the ventral tegmental area after acute and subchronic alcohol administration. In order to compare findings in mice with the human condition, we tested 23 single-nucleotide polymorphisms (SNPs) in the CAMK2A gene for their association with alcohol dependence in a population of 1333 male patients with severe alcohol dependence and 939 controls. We found seven significant associations between CAMK2A SNPs and alcohol dependence, one of which in an autophosphorylation-related area of the gene. Together, our data suggest αCaMKII autophosphorylation as a facilitating mechanism in the establishment of alcohol drinking behavior with changing the DA-5-HT balance as a putative mechanism.

KW - Alcohol Drinking

KW - Alcoholism

KW - Animals

KW - Behavior, Addictive

KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2

KW - Case-Control Studies

KW - Dopamine

KW - Dose-Response Relationship, Drug

KW - Ethanol

KW - Female

KW - Genetic Predisposition to Disease

KW - Humans

KW - Hypnotics and Sedatives

KW - Male

KW - Mice

KW - Motor Activity

KW - Nucleus Accumbens

KW - Phosphorylation

KW - Polymorphism, Single Nucleotide

KW - Prefrontal Cortex

KW - Serotonin

KW - Ventral Tegmental Area

U2 - 10.1038/npp.2013.60

DO - 10.1038/npp.2013.60

M3 - Journal article

C2 - 23459588

VL - 38

SP - 1636

EP - 1647

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

SN - 0893-133X

IS - 9

ER -