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A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens
The transition from occasional to escalated psychostimulant use is accelerated by prior drug exposure. These behavioral observations may be related to long-lasting transcriptional and/or epigenetic changes induced by the drug pre-exposure. Herein, we investigated if a single methamphetamine (METH) i...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060962/ https://www.ncbi.nlm.nih.gov/pubmed/31758400 http://dx.doi.org/10.1007/s12035-019-01830-3 |
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author | Jayanthi, Subramaniam Torres, Oscar V. Ladenheim, Bruce Cadet, Jean Lud |
author_facet | Jayanthi, Subramaniam Torres, Oscar V. Ladenheim, Bruce Cadet, Jean Lud |
author_sort | Jayanthi, Subramaniam |
collection | PubMed |
description | The transition from occasional to escalated psychostimulant use is accelerated by prior drug exposure. These behavioral observations may be related to long-lasting transcriptional and/or epigenetic changes induced by the drug pre-exposure. Herein, we investigated if a single methamphetamine (METH) injection would enhance METH self-administration (SA) and impact any METH SA-induced epigenetic or transcriptional alterations. We thus injected a single METH dose (10 mg/kg) or saline to rats before training them to self-administer METH or saline. There were three experimental groups in SA experiments: (1) a single saline injection followed by saline SA (SS); (2) a single saline injection followed by METH SA (SM); and (3) a single METH injection followed by METH SA (MM). METH-pretreated rats escalated METH SA earlier and took more METH than saline-pretreated animals. Both groups showed similar incubation of cue-induced METH craving. Because compulsive METH takers and METH-abstinent rats show differences in potassium (K(+)) channel mRNA levels in their nucleus accumbens (NAc), we wondered if K(+) channel expression might also help to distinguish between SM and MM groups. We found increases in mRNA and protein expression of shaker-related voltage-gated K(+) channels (Kv1: Kcna1, Kcna3, and Kcna6) and calcium-activated K(+) channels (Kcnn1) in the SM compared to MM rats. SM rats also showed decreased DNA methylation at the CpG-rich sites near the promoter region of Kcna1, Kcna3 and Kcnn1 genes in comparison to MM rats. Together, these results provide additional evidence for potentially using K(+) channels as therapeutic targets against METH use disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-019-01830-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-7060962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-70609622020-03-23 A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens Jayanthi, Subramaniam Torres, Oscar V. Ladenheim, Bruce Cadet, Jean Lud Mol Neurobiol Article The transition from occasional to escalated psychostimulant use is accelerated by prior drug exposure. These behavioral observations may be related to long-lasting transcriptional and/or epigenetic changes induced by the drug pre-exposure. Herein, we investigated if a single methamphetamine (METH) injection would enhance METH self-administration (SA) and impact any METH SA-induced epigenetic or transcriptional alterations. We thus injected a single METH dose (10 mg/kg) or saline to rats before training them to self-administer METH or saline. There were three experimental groups in SA experiments: (1) a single saline injection followed by saline SA (SS); (2) a single saline injection followed by METH SA (SM); and (3) a single METH injection followed by METH SA (MM). METH-pretreated rats escalated METH SA earlier and took more METH than saline-pretreated animals. Both groups showed similar incubation of cue-induced METH craving. Because compulsive METH takers and METH-abstinent rats show differences in potassium (K(+)) channel mRNA levels in their nucleus accumbens (NAc), we wondered if K(+) channel expression might also help to distinguish between SM and MM groups. We found increases in mRNA and protein expression of shaker-related voltage-gated K(+) channels (Kv1: Kcna1, Kcna3, and Kcna6) and calcium-activated K(+) channels (Kcnn1) in the SM compared to MM rats. SM rats also showed decreased DNA methylation at the CpG-rich sites near the promoter region of Kcna1, Kcna3 and Kcnn1 genes in comparison to MM rats. Together, these results provide additional evidence for potentially using K(+) channels as therapeutic targets against METH use disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12035-019-01830-3) contains supplementary material, which is available to authorized users. Springer US 2019-11-22 2020 /pmc/articles/PMC7060962/ /pubmed/31758400 http://dx.doi.org/10.1007/s12035-019-01830-3 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Article Jayanthi, Subramaniam Torres, Oscar V. Ladenheim, Bruce Cadet, Jean Lud A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens |
title | A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens |
title_full | A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens |
title_fullStr | A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens |
title_full_unstemmed | A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens |
title_short | A Single Prior Injection of Methamphetamine Enhances Methamphetamine Self-Administration (SA) and Blocks SA-Induced Changes in DNA Methylation and mRNA Expression of Potassium Channels in the Rat Nucleus Accumbens |
title_sort | single prior injection of methamphetamine enhances methamphetamine self-administration (sa) and blocks sa-induced changes in dna methylation and mrna expression of potassium channels in the rat nucleus accumbens |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060962/ https://www.ncbi.nlm.nih.gov/pubmed/31758400 http://dx.doi.org/10.1007/s12035-019-01830-3 |
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