Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell
A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly in...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/21/11733 |
| _version_ | 1797512400493084672 |
|---|---|
| author | Sheketha R. Hauser Patrick J. Mulholland William A. Truitt R. Aaron Waeiss Eric A. Engleman Richard L. Bell Zachary A. Rodd |
| author_facet | Sheketha R. Hauser Patrick J. Mulholland William A. Truitt R. Aaron Waeiss Eric A. Engleman Richard L. Bell Zachary A. Rodd |
| author_sort | Sheketha R. Hauser |
| collection | DOAJ |
| description | A consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (<i>Chrna7</i>, <i>Impact</i>, <i>Chrna5</i>). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors. |
| first_indexed | 2024-03-10T06:01:17Z |
| format | Article |
| id | doaj.art-00a90f1f1abd4d29b02b013640690ede |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:17Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-00a90f1f1abd4d29b02b013640690ede2023-11-22T20:56:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211173310.3390/ijms222111733Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens ShellSheketha R. Hauser0Patrick J. Mulholland1William A. Truitt2R. Aaron Waeiss3Eric A. Engleman4Richard L. Bell5Zachary A. Rodd6Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Neuroscience, Charleston Alcohol Research Center, Medical University of South Carolina, Charleston, SC 29425, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USADepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAA consistent preclinical finding is that exposure to alcohol during adolescence produces a persistent hyperdopaminergic state during adulthood. The current experiments determine that effects of Adolescent Intermittent Ethanol (AIE) on the adult neurochemical response to EtOH administered directly into the mesolimbic dopamine system, alterations in dendritic spine and gene expression within the nucleus accumbens shell (AcbSh), and if treatment with the HDACII inhibitor TSA could normalize the consequences of AIE. Rats were exposed to the AIE (4 g/kg ig; 3 days a week) or water (CON) during adolescence, and all testing occurred during adulthood. CON and AIE rats were microinjected with EtOH directly into the posterior VTA and dopamine and glutamate levels were recorded in the AcbSh. Separate groups of AIE and CON rats were sacrificed during adulthood and Taqman arrays and dendritic spine morphology assessments were performed. The data indicated that exposure to AIE resulted in a significant leftward and upward shift in the dose-response curve for an increase in dopamine in the AcbSh following EtOH microinjection into the posterior VTA. Taqman array indicated that AIE exposure affected the expression of target genes (<i>Chrna7</i>, <i>Impact</i>, <i>Chrna5</i>). The data indicated no alterations in dendritic spine morphology in the AcbSh or any alteration in AIE effects by TSA administration. Binge-like EtOH exposure during adolescence enhances the response to acute ethanol challenge in adulthood, demonstrating that AIE produces a hyperdopaminergic mesolimbic system in both male and female Wistar rats. The neuroadaptations induced by AIE in the AcbSh could be part of the biological basis of the observed negative consequences of adolescent binge-like alcohol exposure on adult drug self-administration behaviors.https://www.mdpi.com/1422-0067/22/21/11733adolescent alcoholdopamine self-administration |
| spellingShingle | Sheketha R. Hauser Patrick J. Mulholland William A. Truitt R. Aaron Waeiss Eric A. Engleman Richard L. Bell Zachary A. Rodd Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell International Journal of Molecular Sciences adolescent alcohol dopamine self-administration |
| title | Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell |
| title_full | Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell |
| title_fullStr | Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell |
| title_full_unstemmed | Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell |
| title_short | Adolescent Intermittent Ethanol (AIE) Enhances the Dopaminergic Response to Ethanol within the Mesolimbic Pathway during Adulthood: Alterations in Cholinergic/Dopaminergic Genes Expression in the Nucleus Accumbens Shell |
| title_sort | adolescent intermittent ethanol aie enhances the dopaminergic response to ethanol within the mesolimbic pathway during adulthood alterations in cholinergic dopaminergic genes expression in the nucleus accumbens shell |
| topic | adolescent alcohol dopamine self-administration |
| url | https://www.mdpi.com/1422-0067/22/21/11733 |
| work_keys_str_mv | AT sheketharhauser adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell AT patrickjmulholland adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell AT williamatruitt adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell AT raaronwaeiss adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell AT ericaengleman adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell AT richardlbell adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell AT zacharyarodd adolescentintermittentethanolaieenhancesthedopaminergicresponsetoethanolwithinthemesolimbicpathwayduringadulthoodalterationsincholinergicdopaminergicgenesexpressioninthenucleusaccumbensshell |