Parsing Molecular and Behavioral Effects of Cocaine in Mitogen- and Stress-Activated Protein Kinase-1-Deficient Mice

Brami‐Cherrier, Karen; Valjent, Emmanuel; Hervé, Denis; Darragh, Joanne; Corvol, Jean‐Christophe; Pagès, Christiane; Arthur, J. Simon C.; Girault, Jean‐Antoine; Caboche, Jocelyne

doi:10.1523/jneurosci.1711-05.2005

Cited by 269 publications

(305 citation statements)

References 50 publications

Supporting

Mentioning

284

Contrasting

Unclassified

Order By: Relevance

“…DARPP-32 also regulates nuclear events, as demonstrated by alterations of drug-induced gene expression in mice lacking DARPP-32 or bearing a point mutation of Thr-34 12,13 . Part of the control exerted by DARPP-32 on transcription is mediated by activation of the ERK pathway, dependent on the concomitant stimulation of D1R and glutamate NMDA receptors 13,14 . However, the precise mechanisms of information transfer from the cytoplasm to the nucleus of striatal neurons are still poorly characterized.…”

Section: Discussionmentioning

confidence: 99%

“…The phosphorylation of H3 on Ser-10 is a key step in nucleosomal response 28,32 and is crucial for memory formation 33 . It is increased in the striatum after cocaine administration in vivo, and this response is functionally important 14,34 . Cocaine induced an intense phosphoSer-10-H3 signal in the nuclei of a number of striatal neurons in wild type mice, whereas this effect was absent in either T34A-DARPP-32 or S97A-DARPP-32 mice (Fig.5a).…”

Section: Nuclear Translocation Of Darpp-32 Is Essential For D1r-regulmentioning

confidence: 98%

See 1 more Smart Citation

A phosphatase cascade by which rewarding stimuli control nucleosomal response

Stipanovich

Valjent

Matamales

et al. 2008

Nature

217

237

View full text Add to dashboard Cite

SummaryDopamine orchestrates motor behavior and reward-driven learning. Perturbations of dopamine signaling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here, we show that drugs of abuse, as well as natural reinforcement learning, promote the nuclear accumulation of dopamine-and cAMPregulated phosphoprotein Mr=32,000 . This accumulation is mediated through a signaling cascade involving dopamine D1 receptors, cAMP-dependent activation of protein phosphatase-2A, dephosphorylation of DARPP-32 at Ser-97 and inhibition of its nuclear export. The nuclear accumulation of DARPP-32, a potent inhibitor of protein phosphatase-1, increases phosphorylation of histone H3, an important component of nucleosomal response. Mutation of Ser-97 profoundly alters behavioral effects of drugs of abuse, and decreases motivation for food, underlining the functional importance of this signaling cascade.Midbrain dopamine (DA) neurons, activated following unexpected rewarding stimuli, are essential in reinforcement learning 1 . Drugs of abuse mimic the physiological action of DA neurons by increasing their firing rate or preventing DA uptake. Thus, they enhance extracellular DA levels in the forebrain, especially in the nucleus accumbens (NAc), a key structure required for the reinforcing effects of addictive drugs [2][3][4] . To understand how DA mediates reward-controlled learning, it is necessary to identify the intracellular events that trigger gene transcription alterations supporting long-lasting synaptic changes [5][6][7] . DARPP-32 (dopamine-and cAMP-regulated phosphoprotein, Mr=32,000) 8 is a prominent mediator of DA NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript signaling in the striatum 9 . DARPP-32 is highly enriched in striatal GABAergic mediumsize spiny neurons (MSN) 10 . Following activation of DA D1 receptors (D1R), DARPP-32 is phosphorylated by cAMP-dependent protein kinase (PKA) at Thr-34 and converted into a potent inhibitor of the multifunctional serine/threonine protein phosphatase-1 (PP1) 11 . DARPP-32-mediated inhibition of PP1 increases the phosphorylation of neurotransmitter receptors and ion channels crucial for synaptic function and plasticity 9 . DARPP-32 also regulates nuclear events, as demonstrated by alterations of drug-induced gene expression in mice lacking DARPP-32 or bearing a point mutation of 13 . Part of the control exerted by DARPP-32 on transcription is mediated by activation of the ERK pathway, dependent on the concomitant stimulation of D1R and glutamate NMDA receptors 13,14 . However, the precise mechanisms of information transfer from the cytoplasm to the nucleus of striatal neurons are still poorly characterized. Drugs of abuse and reinforcement learning trigger nuclear accumulation of DARPP-32 in striatal neuronsDARPP-32 has been extensively characterized as a cytoplasmic...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Nuclear Translocation Of Darpp-32 Is Essential For D1r-regulmentioning

confidence: 98%

A phosphatase cascade by which rewarding stimuli control nucleosomal response

Stipanovich

Valjent

Matamales

et al. 2008

Nature

217

237

View full text Add to dashboard Cite

show abstract

“…Several studies suggest that dynamic histone acetylation and deacetylation processes are also active in postmitotic neurons [12,20,21,27]. Recently, it has been shown that both acute and chronic cocaine administration are able to induce specific histone modification at different gene promoters in the striatum [6,20,22]. Furthermore, treatment with HDAC inhibitors alter locomotor and rewarding responses to cocaine [20].…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice

Kalda

Heidmets

Shen

et al. 2007

Behavioural Brain Research

View full text Add to dashboard Cite

The behavioral sensitization produced by repeated amphetamine treatment may represent the neural adaptations underlying some of the features of psychosis and addiction in humans. Chromatin modification (specifically histone hyperacetylation) was recently recognized as an important regulator of psychostimulant-induced plasticity. We have investigated the effects of treatment with the histone deacetylase (HDAC) inhibitors butyric acid (BA, 630 mg/kg, i.p) and valproic acid (VPA, 175 mg/kg, i.p.) on the psyhcostimulant locomotor sensitization induced by amphetamine (AMPH, 2.0 mg/kg, i.p.). Neither BA nor VPA had locomotor effects alone, but both significantly potentiated the amphetamine-induced behavioral sensitization in mice. At the molecular level, VPA and amphetamine produced an increase of histone H4 acetylation in the striatum as detected by Western blot analysis, while co-treatment with VPA and AMPH produced an additive effect on histone H4 acetylation. We then administered the HDAC inhibitors after treatment with amphetamine for 8 days to establish locomotor sensitization. We found that repeated administration of VPA or BA for 6 days inhibited the expression of sensitized response following amphetamine challenge. Finally, in a context-specific model we studied the effect of HDAC inhibitors on amphetamine-induced association of the treatment environment (associative learning). We found that VPA and BA enhance the context-specificity of expression of amphetamine sensitization. Thus, HDAC inhibitors differentially modulate the induction and expression of amphetamine-induced effects. Together, these results suggest that dynamic changes in chromatin modification may be an important mechanism underlying amphetamine-induced neuronal plasticity and associative learning.

show abstract

“…For example, Aurora kinases A and B have been demonstrated to catalyze the addition of phosphate groups at H3S10, whereas mitogen-activated protein (MAP) kinase phosphatase-1 has previously been shown to promote the enzymatic removal of phosphate groups at this residue (Pascreau et al, 2003;Kinney et al, 2009). In brain, the dopamine and cAMP regulated protein phosphatase inhibitor, DARPP-32, as well as the MAP kinase, MSK1, provide excellent examples of enzymes regulating H3S10p in response to environmental stimuli, indicating histone phosphorylation as an important regulator of adult neuronal function (Brami-Cherrier et al, 2005;Stipanovich et al, 2008).…”

Section: Histone Phosphorylation and Cross Talk Interactions In The Cnsmentioning

confidence: 99%

Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

Maze

Noh

Allis

2012

Neuropsychopharmacol

117

View full text Add to dashboard Cite

Postmitotic neurons are subject to a vast array of environmental influences that require the nuclear integration of intracellular signaling events to promote a wide variety of neuroplastic states associated with synaptic function, circuit formation, and behavioral memory. Over the last decade, much attention has been paid to the roles of transcription and chromatin regulation in guiding fundamental aspects of neuronal function. A great deal of this work has centered on neurodevelopmental and adulthood plasticity, with increased focus in the areas of neuropharmacology and molecular psychiatry. Here, we attempt to provide a broad overview of chromatin regulation, as it relates to central nervous system (CNS) function, with specific emphasis on the modes of histone posttranslational modifications, chromatin remodeling, and histone variant exchange. Understanding the functions of chromatin in the context of the CNS will aid in the future development of pharmacological therapeutics aimed at alleviating devastating neurological disorders.

show abstract

Parsing Molecular and Behavioral Effects of Cocaine in Mitogen- and Stress-Activated Protein Kinase-1-Deficient Mice

Cited by 269 publications

References 50 publications

A phosphatase cascade by which rewarding stimuli control nucleosomal response

A phosphatase cascade by which rewarding stimuli control nucleosomal response

Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice

Histone Regulation in the CNS: Basic Principles of Epigenetic Plasticity

Contact Info

Product

Resources

About