Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens
Cocaine-induced plasticity in the glutamatergic transmission and its <i>N</i>-methyl-<span style="font-variant: small-caps;">d</span>-aspartate (NMDA) receptors are critically involved in the development of substance use disorder. The presynaptic active zone protein...
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MDPI AG
2020-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/25/15/3480 |
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| author | Irena Smaga Karolina Wydra Małgorzata Frankowska Fabio Fumagalli Marek Sanak Małgorzata Filip |
| author_facet | Irena Smaga Karolina Wydra Małgorzata Frankowska Fabio Fumagalli Marek Sanak Małgorzata Filip |
| author_sort | Irena Smaga |
| collection | DOAJ |
| description | Cocaine-induced plasticity in the glutamatergic transmission and its <i>N</i>-methyl-<span style="font-variant: small-caps;">d</span>-aspartate (NMDA) receptors are critically involved in the development of substance use disorder. The presynaptic active zone proteins control structural synaptic plasticity; however, we are still far from understanding the molecular determinants important for cocaine seeking behavior. The aim of this study was to investigate the effect of cocaine self-administration and different conditions of cocaine forced abstinence on the composition of the NMDA receptor subunits and on the levels of active zone proteins, i.e., Ras-related protein 3A (Rab3A), Rab3 interacting molecules 1 (RIM1) and mammalian uncoordinated protein 13 (Munc13) in the rat nucleus accumbens. We found an up-regulation of the accumbal levels of GluN1 and GluN2A following cocaine self-administration that was paralleled by an increase of Munc13 and RIM1 levels. At the same time, we also demonstrated that different conditions of cocaine abstinence abolished changes in NMDA receptor subunits (except for higher GluN1 levels after cocaine abstinence with extinction training), while an increase in the Munc13 concentration was shown in rats housed in an enriched environment. In conclusion, cocaine self-administration is associated with the specific up-regulation of the NMDA receptor subunit composition and is related with new presynaptic targets controlling neurotransmitter release. Moreover, changes observed in cocaine abstinence with extinction training and in an enriched environment in the levels of NMDA receptor subunit and in the active zone protein, respectively, may represent a potential regulatory step in cocaine-seeking behavior. |
| first_indexed | 2024-03-10T18:04:22Z |
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| id | doaj.art-9146288a891348dd9a0713574821d857 |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T18:04:22Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-9146288a891348dd9a0713574821d8572023-11-20T08:36:51ZengMDPI AGMolecules1420-30492020-07-012515348010.3390/molecules25153480Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus AccumbensIrena Smaga0Karolina Wydra1Małgorzata Frankowska2Fabio Fumagalli3Marek Sanak4Małgorzata Filip5Maj Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, PL 31-343 Kraków, PolandMaj Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, PL 31-343 Kraków, PolandMaj Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, PL 31-343 Kraków, PolandDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti 9, 20133 Milano, ItalyDepartment of Internal Medicine, Jagiellonian University Medical College, Skawińska 8, PL 31-066 Kraków, PolandMaj Institute of Pharmacology Polish Academy of Sciences, Department of Drug Addiction Pharmacology, Smętna 12, PL 31-343 Kraków, PolandCocaine-induced plasticity in the glutamatergic transmission and its <i>N</i>-methyl-<span style="font-variant: small-caps;">d</span>-aspartate (NMDA) receptors are critically involved in the development of substance use disorder. The presynaptic active zone proteins control structural synaptic plasticity; however, we are still far from understanding the molecular determinants important for cocaine seeking behavior. The aim of this study was to investigate the effect of cocaine self-administration and different conditions of cocaine forced abstinence on the composition of the NMDA receptor subunits and on the levels of active zone proteins, i.e., Ras-related protein 3A (Rab3A), Rab3 interacting molecules 1 (RIM1) and mammalian uncoordinated protein 13 (Munc13) in the rat nucleus accumbens. We found an up-regulation of the accumbal levels of GluN1 and GluN2A following cocaine self-administration that was paralleled by an increase of Munc13 and RIM1 levels. At the same time, we also demonstrated that different conditions of cocaine abstinence abolished changes in NMDA receptor subunits (except for higher GluN1 levels after cocaine abstinence with extinction training), while an increase in the Munc13 concentration was shown in rats housed in an enriched environment. In conclusion, cocaine self-administration is associated with the specific up-regulation of the NMDA receptor subunit composition and is related with new presynaptic targets controlling neurotransmitter release. Moreover, changes observed in cocaine abstinence with extinction training and in an enriched environment in the levels of NMDA receptor subunit and in the active zone protein, respectively, may represent a potential regulatory step in cocaine-seeking behavior.https://www.mdpi.com/1420-3049/25/15/3480cocaine abstinencecocaine self-administrationMunc13NMDA receptor subunitRab3ARIM1 |
| spellingShingle | Irena Smaga Karolina Wydra Małgorzata Frankowska Fabio Fumagalli Marek Sanak Małgorzata Filip Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens Molecules cocaine abstinence cocaine self-administration Munc13 NMDA receptor subunit Rab3A RIM1 |
| title | Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens |
| title_full | Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens |
| title_fullStr | Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens |
| title_full_unstemmed | Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens |
| title_short | Cocaine Self-Administration and Abstinence Modulate NMDA Receptor Subunits and Active Zone Proteins in the Rat Nucleus Accumbens |
| title_sort | cocaine self administration and abstinence modulate nmda receptor subunits and active zone proteins in the rat nucleus accumbens |
| topic | cocaine abstinence cocaine self-administration Munc13 NMDA receptor subunit Rab3A RIM1 |
| url | https://www.mdpi.com/1420-3049/25/15/3480 |
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