In vivo microdialysis in awake, freely moving rats demonstrates HIV-1 Tat-induced alterations in dopamine transmission.
Individuals infected with human immunodeficiency virus (HIV) may develop neuropsychological impairment, and a modest percentage may progress to HIV-associated dementia (HAD). Research using human and nonhuman, in vitro and in vivo models, demonstrates that subcortical dopamine (DA) systems may be particularly vulnerable to HIV-induced neurodegeneration. The goal of the current investigation is to provide an understanding of the extent to which the HIV-1 protein Tat induces alterations in striatal DA transmission using in vivo brain microdialysis in awake, freely moving rats. The current study was designed to investigate Tat-induced neuronal dysfunction between 24-h and 48-h post-Tat administration, and demonstrates a reduction in evoked DA for the Tat-treated group relative to vehicle-treated group at 24 and 48 h. The Tat-induced reduction of DA overflow by 24 h suggests dysfunction of nerve terminals, and a compromised DA system in Tat-treated animals. Furthermore, the current study provides direct support for HIV-associated decline of DA function at a systemic level, helping to characterize the functional outcome of the relatively large amount of research on the molecular and behavioral levels of HIV-induced neurotoxicity. This initial study may provide additional characteristics of Tat-induced neuronal dysfunction to inform research on therapeutic intervention, and it provides a springboard for future in vivo research currently needed in the field.
Ferris
Mark J
MJ
Program in Behavioral Neuroscience, Department of Psychology, University of South Carolina, Columbia, SC 29208, USA. mferris@wfubmc.edu
Frederick-Duus
Danielle
D
Fadel
Jim
J
Mactutus
Charles F
CF
Booze
Rosemarie M
RM
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014851:Wakefulness; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism / Q000494:pharmacology*
D054322:tat Gene Products, Human Immunodeficiency Virus; D004298:Dopamine