Abstract
The fronto-striatal circuitry, involving the nucleus accumbens, ventral tegmental area, and prefrontal cortex, mediates goal-directed behavior and is targeted by both drugs of abuse and HIV-1 infection. Acutely, both drugs and HIV-1 provoke increased dopamine activity within the circuit. However, chronic exposure to drugs or HIV-1 leads to dysregulation of the dopamine system as a result of fronto-striatal adaptations to oppose the effects of repeated instances of transiently increased dopamine. Specifically, chronic drug use leads to reduced dopaminergic tone, upregulation of dopamine transporters, and altered circuit connectivity, sending users into an allosteric state in which goal-directed behaviors are dysregulated (i.e., addiction). Similarly, chronic exposure to HIV-1, even with combination antiretroviral therapy (cART), dysregulates dopamine and dopamine transporter function and alters connectivity of the fronto-striatal circuit, contributing to apathy and clinical symptoms of HIV-1 associated neurocognitive disorders (HAND). Thus, in a drug user also exposed to HIV-1, dysregulation of the fronto-striatal dopamine circuit advances at an exacerbated rate and appears to be driven by mechanisms unique from those seen with chronic drug use or HIV-1 exposure alone. We posit that the effects of drug use and HIV-1 infection on microglia interact to drive the progression of motivational dysfunction at an accelerated rate. The current review will therefore explore how the fronto-striatal circuit adapts to drug use (using cocaine as an example), HIV-1 infection, and both together; emphasizing proper methods and providing future directions to develop treatments for pathologies disrupting goal-directed behaviors and improve clinical outcomes for affected patients. [Figure not available: see fulltext.].
Original language | English |
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Pages (from-to) | 715-728 |
Number of pages | 14 |
Journal | Journal of NeuroImmune Pharmacology |
Volume | 15 |
Issue number | 4 |
DOIs | |
State | Published - Dec 2020 |
Bibliographical note
Publisher Copyright:© 2020, Springer Science+Business Media, LLC, part of Springer Nature.
Funding
The authors declare that they have no conflict of interest. Supported by NIH Grants HD043680, MH106392, DA013137, NS100624 and T32 GM081740.
Funders | Funder number |
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National Institutes of Health (NIH) | NS100624, T32 GM081740 |
National Institute of Mental Health | R01MH106392 |
National Institute on Drug Abuse | DA013137 |
National Institute of Neurological Disorders and Stroke | ND100624 |
Eunice Kennedy Shriver National Institute of Child Health and Human Development | HD043680 |
Keywords
- Addiction
- Apathy
- Dopamine
- HIV-1
- HIV-1 associated neurocognitive disorders
- Microglia
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Immunology and Allergy
- Immunology
- Pharmacology