Hyperdopaminergic tone in HIV-1 protein treated rats and cocaine sensitization.
In the United States, one-third of infected individuals contracted Human Immunodeficiency Virus-1 (HIV-1) via injecting drugs with contaminated needles or through risky behaviors associated with drug use. Research demonstrates concomitant administration of psychostimulants and HIV-1-proteins damage neurons to a greater extent than viral proteins or the drug alone. To model the onset of HIV-1-infection in relation to a history of drug use, the current research compared behavior and extracellular dopamine and metabolite levels following Tat(1-86) infusions in animals with and without a history of cocaine (Coc) experience (10 mg/kg; i.p.; 1 injection/day × 9 days). Animals receiving a behaviorally sensitizing regimen of Coc demonstrated a decrease in extracellular dopamine concentration in the nucleus accumbens, consistent with evidence describing up-regulation of dopamine transporter uptake. Contrary to this effect, Tat(1-86) microinfusion into the nucleus accumbens following the sensitizing regimen of Coc caused a significant increase in extracellular dopamine levels (nM) within 48 h with no difference in percent of baseline response to Coc. After 72 h, Tat + Coc treated animals demonstrated a blunted effect on potassium-stimulated extracellular dopamine release (percent of baseline) with a corresponding decrease in expression of behavioral sensitization to Coc challenge. A persistent decrease in extracellular dopamine metabolite levels was found across all time-points in Tat-treated animals, regardless of experience with Coc. The current study provides evidence for divergent neurochemical and behavioral outcomes following Tat-treatment; contingent upon experience with Coc.
Ferris
Mark J
MJ
Program in Behavioral Neuroscience, University of South Carolina, Columbia, South Carolina, USA. mferris@wfubmc.edu
Frederick-Duus
Danielle
D
Fadel
Jim
J
Mactutus
Charles F
CF
Booze
Rosemarie M
RM
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis / Q000502:physiology*; D015497:HIV-1 / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000502:physiology*
D054322:tat Gene Products, Human Immunodeficiency Virus; D003042:Cocaine; D004298:Dopamine
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