Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators
The extant literature supports the role of stress in enhancing the susceptibility of drug abuse progressing to a substance use disorder diagnosis. However, the molecular mediators by which stress enhances the progression from cocaine abuse to cocaine use disorder via the mesolimbic pathway remain el...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Behavioral Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnbeh.2018.00309/full |
| _version_ | 1818137973221228544 |
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| author | Deepika Mukhara Matthew L. Banks Gretchen N. Neigh |
| author_facet | Deepika Mukhara Matthew L. Banks Gretchen N. Neigh |
| author_sort | Deepika Mukhara |
| collection | DOAJ |
| description | The extant literature supports the role of stress in enhancing the susceptibility of drug abuse progressing to a substance use disorder diagnosis. However, the molecular mediators by which stress enhances the progression from cocaine abuse to cocaine use disorder via the mesolimbic pathway remain elusive. In this mini-review article, we highlight three mechanisms by which glucocorticoids (GCs) and the dopaminergic system interact. First, GCs upregulate tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine (DA) synthesis. Second, GCs downregulate monoamine-oxidase (MAO), an enzyme responsible for DA removal. Lastly, GCs are hypothesized to decrease DA reuptake, subsequently increasing synaptic DA. Based on these interactions, we review preclinical literature highlighting how stress modulates the mesolimbic pathway, including the ventral tegmental area (VTA) and nucleus accumbens (NAcs), to alter cocaine abuse-related effects. Taken together, stress enhances cocaine’s abuse-related effects at multiple points along the VTA mesolimbic projection, and uniquely in the NAcs through a positive feedback type mechanism. Furthermore, we highlight future directions to elucidate the interaction between the prefrontal cortex (PFC) and key intermediaries including ΔFosB, cAMP response element binding protein (CREB) and cyclin-dependent kinase 5 (CDK5) to highlight possible mechanisms that underlie stress-induced acceleration of the progression to a cocaine use disorder diagnosis. |
| first_indexed | 2024-12-11T10:04:48Z |
| format | Article |
| id | doaj.art-02f735b0981b41ceb162ef3cfea0dffd |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-11T10:04:48Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-02f735b0981b41ceb162ef3cfea0dffd2022-12-22T01:12:00ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532018-12-011210.3389/fnbeh.2018.00309410828Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular MediatorsDeepika Mukhara0Matthew L. Banks1Gretchen N. Neigh2Department of Anatomy & Neurobiology, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA, United StatesDepartment of Anatomy & Neurobiology, Virginia Commonwealth University, Richmond, VA, United StatesThe extant literature supports the role of stress in enhancing the susceptibility of drug abuse progressing to a substance use disorder diagnosis. However, the molecular mediators by which stress enhances the progression from cocaine abuse to cocaine use disorder via the mesolimbic pathway remain elusive. In this mini-review article, we highlight three mechanisms by which glucocorticoids (GCs) and the dopaminergic system interact. First, GCs upregulate tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine (DA) synthesis. Second, GCs downregulate monoamine-oxidase (MAO), an enzyme responsible for DA removal. Lastly, GCs are hypothesized to decrease DA reuptake, subsequently increasing synaptic DA. Based on these interactions, we review preclinical literature highlighting how stress modulates the mesolimbic pathway, including the ventral tegmental area (VTA) and nucleus accumbens (NAcs), to alter cocaine abuse-related effects. Taken together, stress enhances cocaine’s abuse-related effects at multiple points along the VTA mesolimbic projection, and uniquely in the NAcs through a positive feedback type mechanism. Furthermore, we highlight future directions to elucidate the interaction between the prefrontal cortex (PFC) and key intermediaries including ΔFosB, cAMP response element binding protein (CREB) and cyclin-dependent kinase 5 (CDK5) to highlight possible mechanisms that underlie stress-induced acceleration of the progression to a cocaine use disorder diagnosis.https://www.frontiersin.org/article/10.3389/fnbeh.2018.00309/fullstressaddictioncocaineVTANAcdrugs |
| spellingShingle | Deepika Mukhara Matthew L. Banks Gretchen N. Neigh Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators Frontiers in Behavioral Neuroscience stress addiction cocaine VTA NAc drugs |
| title | Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators |
| title_full | Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators |
| title_fullStr | Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators |
| title_full_unstemmed | Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators |
| title_short | Stress as a Risk Factor for Substance Use Disorders: A Mini-Review of Molecular Mediators |
| title_sort | stress as a risk factor for substance use disorders a mini review of molecular mediators |
| topic | stress addiction cocaine VTA NAc drugs |
| url | https://www.frontiersin.org/article/10.3389/fnbeh.2018.00309/full |
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