Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration
Methamphetamine (METH) use disorder affects both sexes, with sex differences occurring in behavioral, structural, and biochemical consequences. The molecular mechanisms underlying these differences are unclear. Herein, we used a rat model to identify potential sex differences in the effects of METH...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/8/4353 |
| _version_ | 1797434552153538560 |
|---|---|
| author | Atul P. Daiwile Patricia Sullivan Subramaniam Jayanthi David S. Goldstein Jean Lud Cadet |
| author_facet | Atul P. Daiwile Patricia Sullivan Subramaniam Jayanthi David S. Goldstein Jean Lud Cadet |
| author_sort | Atul P. Daiwile |
| collection | DOAJ |
| description | Methamphetamine (METH) use disorder affects both sexes, with sex differences occurring in behavioral, structural, and biochemical consequences. The molecular mechanisms underlying these differences are unclear. Herein, we used a rat model to identify potential sex differences in the effects of METH on brain dopaminergic systems. Rats were trained to self-administer METH for 20 days, and a cue-induced drug-seeking test was performed on withdrawal days 3 and 30. Dopamine and its metabolites were measured in the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (dSTR), and hippocampus (HIP). Irrespective of conditions, in comparison to females, male rats showed increased 3,4-dihydroxyphenylalanine (DOPA) in the PFC, dSTR, and HIP; increased cys-dopamine in NAc; and increased 3,4-dihydroxyphenylethanol (DOPET) and 3,4-dihydroxyphenylacetic acid (DOPAC) in dSTR. Males also showed METH-associated decreases in DA levels in the HIP but increases in the NAc. Female rats showed METH-associated decreases in DA, DOPAL, and DOPAC levels in the PFC but increases in DOPET and DOPAC levels in the HIP. Both sexes showed METH-associated decreases in NAc DA metabolites. Together, these data document sex differences in METH SA-induced changes in DA metabolism. These observations provide further support for using sex as an essential variable when discussing therapeutic approaches against METH use disorder in humans. |
| first_indexed | 2024-03-09T10:33:57Z |
| format | Article |
| id | doaj.art-426b6286b1984cce848d38ba1c903148 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:33:57Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-426b6286b1984cce848d38ba1c9031482023-12-01T21:04:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238435310.3390/ijms23084353Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-AdministrationAtul P. Daiwile0Patricia Sullivan1Subramaniam Jayanthi2David S. Goldstein3Jean Lud Cadet4Molecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, National Institutes of Health (NIH), Baltimore, MD 21224, USAAutonomic Medicine Section, NINDS Intramural Research Program, National Institutes of Health (NIH), Bethesda, MD 20892, USAMolecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, National Institutes of Health (NIH), Baltimore, MD 21224, USAAutonomic Medicine Section, NINDS Intramural Research Program, National Institutes of Health (NIH), Bethesda, MD 20892, USAMolecular Neuropsychiatry Research Branch, NIDA Intramural Research Program, National Institutes of Health (NIH), Baltimore, MD 21224, USAMethamphetamine (METH) use disorder affects both sexes, with sex differences occurring in behavioral, structural, and biochemical consequences. The molecular mechanisms underlying these differences are unclear. Herein, we used a rat model to identify potential sex differences in the effects of METH on brain dopaminergic systems. Rats were trained to self-administer METH for 20 days, and a cue-induced drug-seeking test was performed on withdrawal days 3 and 30. Dopamine and its metabolites were measured in the prefrontal cortex (PFC), nucleus accumbens (NAc), dorsal striatum (dSTR), and hippocampus (HIP). Irrespective of conditions, in comparison to females, male rats showed increased 3,4-dihydroxyphenylalanine (DOPA) in the PFC, dSTR, and HIP; increased cys-dopamine in NAc; and increased 3,4-dihydroxyphenylethanol (DOPET) and 3,4-dihydroxyphenylacetic acid (DOPAC) in dSTR. Males also showed METH-associated decreases in DA levels in the HIP but increases in the NAc. Female rats showed METH-associated decreases in DA, DOPAL, and DOPAC levels in the PFC but increases in DOPET and DOPAC levels in the HIP. Both sexes showed METH-associated decreases in NAc DA metabolites. Together, these data document sex differences in METH SA-induced changes in DA metabolism. These observations provide further support for using sex as an essential variable when discussing therapeutic approaches against METH use disorder in humans.https://www.mdpi.com/1422-0067/23/8/4353methamphetaminesex differencesdopamineDA metabolitesmesocorticolimbic |
| spellingShingle | Atul P. Daiwile Patricia Sullivan Subramaniam Jayanthi David S. Goldstein Jean Lud Cadet Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration International Journal of Molecular Sciences methamphetamine sex differences dopamine DA metabolites mesocorticolimbic |
| title | Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration |
| title_full | Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration |
| title_fullStr | Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration |
| title_full_unstemmed | Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration |
| title_short | Sex-Specific Alterations in Dopamine Metabolism in the Brain after Methamphetamine Self-Administration |
| title_sort | sex specific alterations in dopamine metabolism in the brain after methamphetamine self administration |
| topic | methamphetamine sex differences dopamine DA metabolites mesocorticolimbic |
| url | https://www.mdpi.com/1422-0067/23/8/4353 |
| work_keys_str_mv | AT atulpdaiwile sexspecificalterationsindopaminemetabolisminthebrainaftermethamphetamineselfadministration AT patriciasullivan sexspecificalterationsindopaminemetabolisminthebrainaftermethamphetamineselfadministration AT subramaniamjayanthi sexspecificalterationsindopaminemetabolisminthebrainaftermethamphetamineselfadministration AT davidsgoldstein sexspecificalterationsindopaminemetabolisminthebrainaftermethamphetamineselfadministration AT jeanludcadet sexspecificalterationsindopaminemetabolisminthebrainaftermethamphetamineselfadministration |