Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca<sup>2+</sup>-Dependent Manner

Kim, Jieun; Ryu, In Soo; Seo, Seungwan; Choe, Eun Sang

doi:10.1093/ijnp/pyv075

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…The dorsomedial striatum (DMS) is an important brain region for the transition to addiction from initial to compulsive use Caprioli et al, 2017). Within the dorsal striatum, cocaine exposure produces a number of changes to intracellular signaling cascades, in part by modulating regulation of calcium (Yang & Choe, 2014;Kim et al, 2015;Kim et al, 2009;Schierberl et al, 2012;Shen et al, 2018). In addition, intracellular calcium signaling in the striatum modulates cocaine reward and sensitization (Barr et al, 2015;Mizuno et al, 2013;Yasui and Su, 2016).…”

Section: Introductionmentioning

confidence: 99%

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats

García¹,

Webb²,

Yager³

et al. 2020

Psychopharmacology

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Drug addiction is a chronic disease defined by a complex set of characteristics, including loss of control over drug intake and persistent drug craving, which primarily affects a small percentage of people who try drugs. Although many models have been developed to study individual aspects of drug use, there is great translational value in having an animal model that encompasses multiple aspects of the human disease, including the variation in severity observed in humans. Here, we describe an intermittent access model of cocaine self-administration that produces a subset of rats that display many of the core features of addiction, including escalation of drug intake, a bingelike pattern of drug use, robust locomotor sensitization, and high levels of drug-seeking during cue-induced reinstatement. This group is compared to rats that have the same drug history but do not develop this pattern of drug-taking and drug-seeking, as well as rats that undergo a traditional continuous access paradigm. Finally, we observe that high levels of cocaine consumption produce long-term changes in intracellular calcium signaling in the dorsomedial striatum.Terms of use and reuse: academic research for non-commercial purposes, see here for full terms. http://www.springer.com/gb/openaccess/authors-rights/aam-terms-v1

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Section: Introductionmentioning

confidence: 99%

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats

García¹,

Webb²,

Yager³

et al. 2020

Psychopharmacology

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“…Another complexity of calcium regulation is the calcium activation effect on protein kinase C (PKC) and Ca 2+ /calmodulin-dependent protein kinase II (CaMK II). Activation of these kinases also results in DARPP32-Thr75 phosphorylation [ 49 ]. Therefore, different protein kinases and phosphatases activated by glutamate receptors dynamically modulate the phosphorylation of DARPP32-Thr75 site [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

“…Activation of these kinases also results in DARPP32-Thr75 phosphorylation [ 49 ]. Therefore, different protein kinases and phosphatases activated by glutamate receptors dynamically modulate the phosphorylation of DARPP32-Thr75 site [ 49 ].…”

Section: Introductionmentioning

confidence: 99%

The involvement of DARPP-32 in the pathophysiology of schizophrenia

et al. 2017

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Schizophrenia is one of the most devastating heterogeneous psychiatric disorders. The dopamine hypothesis is the longest standing pathoetiologic theory of schizophrenia based on neurochemical evidences of elevated brain striatal dopamine synthesis capacity and increased dopamine release in response to stress. Dopamine and cyclic AMP-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) is a cytosolic protein highly enriched in the medium spiny neurons of the neostriatum, considered as the most important integrator between the cortical input and the basal ganglia, and associated with motor control. Accumulating evidences has indicated the involvement of DARPP-32 in the development of schizophrenia; i. DARPP-32 phosphorylation is regulated by several neurotransmitters, including dopamine and glutamate, neurotransmitters implicated in schizophrenia pathogenesis; ii. decrease of both total and phosphorylated DARPP-32 in the prefrontal cortex are observed in schizophrenic animal models; iii. postmortem brain studies indicated decreased expression of DARPP-32 protein in the superior temporal gyrus and dorsolateral prefrontal cortex in patients with schizophrenia; iv. DARPP-32 phosphorylation is increased upon therapy with antipsychotic drugs, such as haloperidol and risperidone which improve behavioral performance in experimental animal models and patients; v. Genetic analysis of the gene coding for DARPP-32 propose an association with schizophrenia. Cumulatively, these findings implicate DARPP-32 protein in schizophrenia and propose it as a potential therapeutic target. Here, we summarize the possible roles of DARPP-32 during the development of schizophrenia and make some recommendations for future research. We propose that DARPP-32 and its interacting proteins may serve as potential therapeutic targets in the treatment of schizophrenia.

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“…Parallel to the activation of protein kinases, an increase in protein phosphatase activity regulates the phosphorylation state of substrates and downstream protein kinases by dephosphorylating them in the CPu of rats after repeated cocaine administration. 34 The interaction of JNK and mGluR5 is further controlled by the activities of PP1/2A and PP2B as demonstrated by the present finding that inhibition of them increases the interaction in the CPu of rat after repeated cocaine administration.…”

Section: Discussionmentioning

confidence: 61%

Interaction of JNK and mGluR5 in the regulation of psychomotor behaviours after repeated cocaine administration

et al. 2022

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Activation of protein kinases after cocaine administration controls psychomotor behaviours by interacting with metabotropic receptors in the brain. This study identified how c-Jun N-terminal kinase (JNK) interacts with metabotropic glutamate receptor 5 (mGluR5) in vitro and in the caudate and putamen (CPu). The potential role of this interaction in the regulation of psychomotor behaviour was also evaluated after administration of cocaine. Active JNK phosphorylates a threonine residue at position 1055 in the carboxyl terminus (CT) of mGluR5 in vitro. The binding of active JNK to the D-motif within CT2 is necessary for that phosphorylation.Interaction of phosphorylated JNK and mGluR5 occurs in the CPu. Unilateral interference of the interaction decreases the repeated cocaine-induced increases in locomotor activity and conditioned place preference. These findings suggest that activation of JNK has the capability to interact with mGluR5 in the CPu. Phosphorylation of mGluR5 following the JNK-mGluR5 interaction may be responsible for the potentiation of behavioural sensitisation and cocaine-wanting behaviour in response to cocaine administration.

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Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca²⁺-Dependent Manner

Cited by 7 publications

References 43 publications

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats

The involvement of DARPP-32 in the pathophysiology of schizophrenia

Interaction of JNK and mGluR5 in the regulation of psychomotor behaviours after repeated cocaine administration

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Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca2+-Dependent Manner

Cited by 7 publications

References 43 publications

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats

Intermittent but not continuous access to cocaine produces individual variability in addiction susceptibility in rats

The involvement of DARPP-32 in the pathophysiology of schizophrenia

Interaction of JNK and mGluR5 in the regulation of psychomotor behaviours after repeated cocaine administration

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Activation of Protein Kinases and Phosphatases Coupled to Glutamate Receptors Regulates the Phosphorylation State of DARPP32 at Threonine 75 After Repeated Exposure to Cocaine in the Rat Dorsal Striatum in a Ca²⁺-Dependent Manner