Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway
Cocaine administration alters the microRNA (miRNA) landscape in the cortico-accumbal pathway. These changes in miRNA can play a major role in the posttranscriptional regulation of gene expression during withdrawal. This study aimed to investigate the changes in microRNA expression in the cortico-acc...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/5/1368 |
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| author | Vidhya Kumaresan Yolpanhchana Lim Poorva Juneja Allison E. Tipton Giordano de Guglielmo Lieselot L. G. Carrette Marsida Kallupi Lisa Maturin Ying Liu Olivier George Huiping Zhang |
| author_facet | Vidhya Kumaresan Yolpanhchana Lim Poorva Juneja Allison E. Tipton Giordano de Guglielmo Lieselot L. G. Carrette Marsida Kallupi Lisa Maturin Ying Liu Olivier George Huiping Zhang |
| author_sort | Vidhya Kumaresan |
| collection | DOAJ |
| description | Cocaine administration alters the microRNA (miRNA) landscape in the cortico-accumbal pathway. These changes in miRNA can play a major role in the posttranscriptional regulation of gene expression during withdrawal. This study aimed to investigate the changes in microRNA expression in the cortico-accumbal pathway during acute withdrawal and protracted abstinence following escalated cocaine intake. Small RNA sequencing (sRNA-seq) was used to profile miRNA transcriptomic changes in the cortico-accumbal pathway [infralimbic- and prelimbic-prefrontal cortex (IL and PL) and nucleus accumbens (NAc)] of rats with extended access to cocaine self-administration followed by an 18-h withdrawal or a 4-week abstinence. An 18-h withdrawal led to differential expression (fold-change > 1.5 and <i>p</i> < 0.05) of 21 miRNAs in the IL, 18 miRNAs in the PL, and two miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in the following pathways: <i>gap junctions</i>, <i>neurotrophin signaling</i>, <i>MAPK signaling</i>, and <i>cocaine addiction</i>. Moreover, a 4-week abstinence led to differential expression (fold-change > 1.5 and <i>p</i> < 0.05) of 23 miRNAs in the IL, seven in the PL, and five miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in pathways including <i>gap junctions</i>, <i>cocaine addiction</i>, <i>MAPK signaling</i>, <i>glutamatergic synapse</i>, <i>morphine addiction</i>, and <i>amphetamine addiction</i>. Additionally, the expression levels of several miRNAs differentially expressed in either the IL or the NAc were significantly correlated with addiction behaviors. Our findings highlight the impact of acute and protracted abstinence from escalated cocaine intake on miRNA expression in the cortico-accumbal pathway, a key circuit in addiction, and suggest developing novel biomarkers and therapeutic approaches to prevent relapse by targeting abstinence-associated miRNAs and their regulated mRNAs. |
| first_indexed | 2024-03-11T03:54:55Z |
| format | Article |
| id | doaj.art-8facc207eb9243c3acc94efbec4c16dd |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:54:55Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-8facc207eb9243c3acc94efbec4c16dd2023-11-18T00:36:01ZengMDPI AGBiomedicines2227-90592023-05-01115136810.3390/biomedicines11051368Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal PathwayVidhya Kumaresan0Yolpanhchana Lim1Poorva Juneja2Allison E. Tipton3Giordano de Guglielmo4Lieselot L. G. Carrette5Marsida Kallupi6Lisa Maturin7Ying Liu8Olivier George9Huiping Zhang10Department of Pharmacology, Physiology & Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Psychiatry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Psychiatry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Pharmacology, Physiology & Biophysics, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USADepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USADepartment of Psychiatry, Boston University Chobanian and Avedisian School of Medicine, Boston, MA 02118, USACocaine administration alters the microRNA (miRNA) landscape in the cortico-accumbal pathway. These changes in miRNA can play a major role in the posttranscriptional regulation of gene expression during withdrawal. This study aimed to investigate the changes in microRNA expression in the cortico-accumbal pathway during acute withdrawal and protracted abstinence following escalated cocaine intake. Small RNA sequencing (sRNA-seq) was used to profile miRNA transcriptomic changes in the cortico-accumbal pathway [infralimbic- and prelimbic-prefrontal cortex (IL and PL) and nucleus accumbens (NAc)] of rats with extended access to cocaine self-administration followed by an 18-h withdrawal or a 4-week abstinence. An 18-h withdrawal led to differential expression (fold-change > 1.5 and <i>p</i> < 0.05) of 21 miRNAs in the IL, 18 miRNAs in the PL, and two miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in the following pathways: <i>gap junctions</i>, <i>neurotrophin signaling</i>, <i>MAPK signaling</i>, and <i>cocaine addiction</i>. Moreover, a 4-week abstinence led to differential expression (fold-change > 1.5 and <i>p</i> < 0.05) of 23 miRNAs in the IL, seven in the PL, and five miRNAs in the NAc. The mRNAs potentially targeted by these miRNAs were enriched in pathways including <i>gap junctions</i>, <i>cocaine addiction</i>, <i>MAPK signaling</i>, <i>glutamatergic synapse</i>, <i>morphine addiction</i>, and <i>amphetamine addiction</i>. Additionally, the expression levels of several miRNAs differentially expressed in either the IL or the NAc were significantly correlated with addiction behaviors. Our findings highlight the impact of acute and protracted abstinence from escalated cocaine intake on miRNA expression in the cortico-accumbal pathway, a key circuit in addiction, and suggest developing novel biomarkers and therapeutic approaches to prevent relapse by targeting abstinence-associated miRNAs and their regulated mRNAs.https://www.mdpi.com/2227-9059/11/5/1368protracted abstinenceoutbred heterogeneous stock ratsprefrontal cortexnucleus accumbensrat brain miRNAsmall RNA sequencing |
| spellingShingle | Vidhya Kumaresan Yolpanhchana Lim Poorva Juneja Allison E. Tipton Giordano de Guglielmo Lieselot L. G. Carrette Marsida Kallupi Lisa Maturin Ying Liu Olivier George Huiping Zhang Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway Biomedicines protracted abstinence outbred heterogeneous stock rats prefrontal cortex nucleus accumbens rat brain miRNA small RNA sequencing |
| title | Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway |
| title_full | Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway |
| title_fullStr | Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway |
| title_full_unstemmed | Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway |
| title_short | Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway |
| title_sort | abstinence from escalation of cocaine intake changes the microrna landscape in the cortico accumbal pathway |
| topic | protracted abstinence outbred heterogeneous stock rats prefrontal cortex nucleus accumbens rat brain miRNA small RNA sequencing |
| url | https://www.mdpi.com/2227-9059/11/5/1368 |
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