HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function

Kesby, James P., Najera, Julia A., Romoli, Benedetto, Fang, Yiding, Basova, Liana, Birmingham, Amanda, Marcondes, Maria Cecilia G., Dulcis, Davide and Semenova, Svetlana (2017) HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function. Brain Behavior and Immunity, 65 210-221. doi:10.1016/j.bbi.2017.05.004

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Author Kesby, James P.
Najera, Julia A.
Romoli, Benedetto
Fang, Yiding
Basova, Liana
Birmingham, Amanda
Marcondes, Maria Cecilia G.
Dulcis, Davide
Semenova, Svetlana
Title HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function
Journal name Brain Behavior and Immunity   Check publisher's open access policy
ISSN 1090-2139
Publication date 2017-10-01
Year available 2017
Sub-type Article (original research)
DOI 10.1016/j.bbi.2017.05.004
Open Access Status File (Author Post-print)
Volume 65
Start page 210
End page 221
Total pages 12
Place of publication Maryland Heights, MO United States
Publisher Academic Press
Language eng
Subject 2403 Immunology
2807 Endocrine and Autonomic Systems
2802 Behavioral Neuroscience
Abstract Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period. Dopamine function in the nucleus accumbens (Acb) was determined using high performance liquid chromatography. Expression of dopamine and/or adenosine A receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR and immunohistochemistry analyses. Microarrays with pathway analyses assessed dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter switching of a reserve pool of non-dopaminergic neurons to a dopaminergic phenotype in the ventral tegmental area (VTA) was determined by immunohistochemistry and quantified with stereology. TAT expression enhanced methamphetamine-induced sensitization. TAT expression alone decreased striatal dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing ADORA2A receptors expression. Moreover, TAT expression combined with methamphetamine exposure was associated with increased adenosine A receptors (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA. TAT expression and methamphetamine exposure induced microglia activation with the largest effect after combined exposure. Our findings suggest that dopamine-adenosine receptor interactions and reserve pool neuronal recruitment may represent potential targets to develop new treatments for methamphetamine abuse in individuals with HIV.
Keyword TAT expression
Locomotor activity
Dopamine receptors
Adenosine receptors
Brain neurochemistry
Gene expression microarrays
Neurotransmitter respecification
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID R03 DA033849
P50 DA026306
R25 MH081482
UL1 TR001442
R01 DA036164
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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