Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation
Abstract Spinophilin is a scaffolding protein enriched in dendritic spines with integral roles in the regulation of spine density and morphology, and the modulation of synaptic plasticity. The ability of spinophilin to alter synaptic strength appears to involve its scaffolding of key synaptic protei...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Molecular Brain |
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| Online Access: | http://link.springer.com/article/10.1186/s13041-019-0434-7 |
| _version_ | 1818447495144931328 |
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| author | Lorena Bianchine Areal Alison Hamilton Cristina Martins-Silva Rita Gomes Wanderley Pires Stephen S. G. Ferguson |
| author_facet | Lorena Bianchine Areal Alison Hamilton Cristina Martins-Silva Rita Gomes Wanderley Pires Stephen S. G. Ferguson |
| author_sort | Lorena Bianchine Areal |
| collection | DOAJ |
| description | Abstract Spinophilin is a scaffolding protein enriched in dendritic spines with integral roles in the regulation of spine density and morphology, and the modulation of synaptic plasticity. The ability of spinophilin to alter synaptic strength appears to involve its scaffolding of key synaptic proteins, including the important structural element F-actin, AMPA/NMDA modulator protein phosphatase 1, and neuromodulatory G-protein coupled receptors, including dopamine receptor D2 and metabotropic glutamate receptor 5. Additionally, spinophilin is highly expressed in the striatum, a brain region that is fundamentally involved in reward-processing and locomotor activity which receives both glutamatergic and dopaminergic inputs. Therefore, we aimed to investigate the role of spinophilin in behavioral responses to cocaine, evaluating wild-type and spinophilin knockout mice followed by the examination of underlying molecular alterations. Although acute locomotor response was not affected, deletion of spinophilin blocked the development and expression of behavioral sensitization to cocaine while maintaining normal conditioned place preference. This behavioral alteration in spinophilin knockout mice was accompanied by attenuated c-Fos and ∆FosB expression following cocaine administration and blunted cocaine-induced phosphorylation of ERK1/2 in the striatum, with no change in other relevant signaling molecules. Therefore, we suggest spinophilin fulfills an essential role in cocaine-induced behavioral sensitization, likely via ERK1/2 phosphorylation and induction of c-Fos and ∆FosB in the striatum, a mechanism that may underlie specific processes in cocaine addiction. |
| first_indexed | 2024-12-14T20:04:31Z |
| format | Article |
| id | doaj.art-3ee03a5810d64af880c278a3e8e87c22 |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-14T20:04:31Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-3ee03a5810d64af880c278a3e8e87c222022-12-21T22:49:04ZengBMCMolecular Brain1756-66062019-02-0112111610.1186/s13041-019-0434-7Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activationLorena Bianchine Areal0Alison Hamilton1Cristina Martins-Silva2Rita Gomes Wanderley Pires3Stephen S. G. Ferguson4Department of Cellular and Molecular Medicine and University of Ottawa Brain and Mind Institute, University of OttawaDepartment of Cellular and Molecular Medicine and University of Ottawa Brain and Mind Institute, University of OttawaDepartment of Physiological Sciences, Health Sciences Center, Federal University of Espirito, SantoGraduate Program in Neuroscience, Institute of Biological Sciences, Federal University of Minas GeraisDepartment of Cellular and Molecular Medicine and University of Ottawa Brain and Mind Institute, University of OttawaAbstract Spinophilin is a scaffolding protein enriched in dendritic spines with integral roles in the regulation of spine density and morphology, and the modulation of synaptic plasticity. The ability of spinophilin to alter synaptic strength appears to involve its scaffolding of key synaptic proteins, including the important structural element F-actin, AMPA/NMDA modulator protein phosphatase 1, and neuromodulatory G-protein coupled receptors, including dopamine receptor D2 and metabotropic glutamate receptor 5. Additionally, spinophilin is highly expressed in the striatum, a brain region that is fundamentally involved in reward-processing and locomotor activity which receives both glutamatergic and dopaminergic inputs. Therefore, we aimed to investigate the role of spinophilin in behavioral responses to cocaine, evaluating wild-type and spinophilin knockout mice followed by the examination of underlying molecular alterations. Although acute locomotor response was not affected, deletion of spinophilin blocked the development and expression of behavioral sensitization to cocaine while maintaining normal conditioned place preference. This behavioral alteration in spinophilin knockout mice was accompanied by attenuated c-Fos and ∆FosB expression following cocaine administration and blunted cocaine-induced phosphorylation of ERK1/2 in the striatum, with no change in other relevant signaling molecules. Therefore, we suggest spinophilin fulfills an essential role in cocaine-induced behavioral sensitization, likely via ERK1/2 phosphorylation and induction of c-Fos and ∆FosB in the striatum, a mechanism that may underlie specific processes in cocaine addiction.http://link.springer.com/article/10.1186/s13041-019-0434-7Drug addictionSpinophilinCocaineBehavioral sensitization |
| spellingShingle | Lorena Bianchine Areal Alison Hamilton Cristina Martins-Silva Rita Gomes Wanderley Pires Stephen S. G. Ferguson Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation Molecular Brain Drug addiction Spinophilin Cocaine Behavioral sensitization |
| title | Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation |
| title_full | Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation |
| title_fullStr | Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation |
| title_full_unstemmed | Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation |
| title_short | Neuronal scaffolding protein spinophilin is integral for cocaine-induced behavioral sensitization and ERK1/2 activation |
| title_sort | neuronal scaffolding protein spinophilin is integral for cocaine induced behavioral sensitization and erk1 2 activation |
| topic | Drug addiction Spinophilin Cocaine Behavioral sensitization |
| url | http://link.springer.com/article/10.1186/s13041-019-0434-7 |
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