HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time.

Autor: Lark ARS; Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA., Nass SR; Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA., Hahn YK; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA., Gao B; Neurochemistry Core, Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, USA., Milne GL; Neurochemistry Core, Vanderbilt Brain Institute, Vanderbilt University, Nashville, Tennessee, USA., Knapp PE; Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA.; Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia, USA., Hauser KF; Department of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.; Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia, USA.; Institute for Drug and Alcohol Studies, Virginia Commonwealth University, Richmond, Virginia, USA.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Mar; Vol. 168 (3), pp. 185-204. Date of Electronic Publication: 2024 Feb 03.
DOI: 10.1111/jnc.16057
Abstrakt: Despite the advent of combination anti-retroviral therapy (cART), nearly half of people infected with HIV treated with cART still exhibit HIV-associated neurocognitive disorders (HAND). HAND can be worsened by co-morbid opioid use disorder. The basal ganglia are particularly vulnerable to HIV-1 and exhibit higher viral loads and more severe pathology, which can be exacerbated by co-exposure to opioids. Evidence suggests that dopaminergic neurotransmission is disrupted by HIV exposure, however, little is known about whether co-exposure to opioids may alter neurotransmitter levels in the striatum and if this in turn influences behavior. Therefore, we assayed motor, anxiety-like, novelty-seeking, exploratory, and social behaviors, and levels of monoamines and their metabolites following 2 weeks and 2 months of Tat and/or morphine exposure in transgenic mice. Morphine decreased dopamine levels, but significantly elevated norepinephrine, the dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the serotonin metabolite 5-hydroxyindoleacetic acid, which typically correlated with increased locomotor behavior. The combination of Tat and morphine altered dopamine, DOPAC, and HVA concentrations differently depending on the neurotransmitter/metabolite and duration of exposure but did not affect the numbers of tyrosine hydroxylase-positive neurons in the mesencephalon. Tat exposure increased the latency to interact with novel conspecifics, but not other novel objects, suggesting the viral protein inhibits exploratory behavior initiation in a context-dependent manner. By contrast, and consistent with prior findings that opioid misuse can increase novelty-seeking behavior, morphine exposure increased the time spent exploring a novel environment. Finally, Tat and morphine interacted to affect locomotor activity in a time-dependent manner, while grip strength and rotarod performance were unaffected. Together, our results provide novel insight into the unique effects of HIV-1 Tat and morphine on monoamine neurochemistry that may underlie their divergent effects on motor and exploratory behavior.
(© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
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