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Biochemical Neuroadaptations in the Rat Striatal Dopaminergic System after Prolonged Exposure to Methamphetamine Self-Administration.
- Source :
- International Journal of Molecular Sciences; Sep2022, Vol. 23 Issue 17, p10092, 20p
- Publication Year :
- 2022
-
Abstract
- Perturbations in striatal dopamine (DA) homeostasis might underlie the behavioral and pathobiological consequences of METH use disorder in humans. To identify potential consequences of long-term METH exposure, we modeled the adverse consequence DSM criterion of substance use disorders by giving footshocks to rats that had escalated their intake of METH during a drug self-administration procedure. Next, DA D1 receptor antagonist, SCH23390 was injected. Thereafter, rats were euthanized to measure several indices of the striatal dopaminergic system. Footshocks split the METH rats into two phenotypes: (i) shock-sensitive that decreased their METH-intake and (ii) shock-resistant that continued their METH intake. SCH23390 caused substantial dose-dependent reduction of METH taking in both groups. Stopping SCH23390 caused re-emergence of compulsive METH taking in shock-resistant rats. Compulsive METH takers also exhibited greater incubation of METH seeking than non-compulsive rats during withdrawal from METH SA. Analyses of DA metabolism revealed non-significant decreases (about 35%) in DA levels in resistant and sensitive rats. However, striatal contents of the deaminated metabolites, DOPAL and DOPAC, were significantly increased in sensitive rats. VMAT2 and DAT protein levels were decreased in both phenotypes. Moreover, protein expression levels of the D1-like DA receptor, D5R, and D2-like DA receptors, D3R and D4R, were significantly decreased in the compulsive METH takers. Our results parallel findings in post-mortem striatal tissues of human METH users who develop Parkinsonism after long-term METH intake and support the use of this model to investigate potential therapeutic interventions for METH use disorder. [ABSTRACT FROM AUTHOR]
- Subjects :
- DOPAMINE receptors
RATS
METHAMPHETAMINE
PROTEIN expression
SUBSTANCE abuse
Subjects
Details
- Language :
- English
- ISSN :
- 16616596
- Volume :
- 23
- Issue :
- 17
- Database :
- Complementary Index
- Journal :
- International Journal of Molecular Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 159011134
- Full Text :
- https://doi.org/10.3390/ijms231710092