Increased dopaminergic neurotransmission in therapy-naïve asymptomatic HIV patients is not associated with adaptive changes at the dopaminergic synapses.
Central dopaminergic (DA) systems are affected during human immunodeficiency virus (HIV) infection. So far, it is believed that they degenerate with progression of HIV disease because deterioration of DA systems is evident in advanced stages of infection. In this manuscript we found that (a) DA levels are increased and DA turnover is decreased in CSF of therapy-naïve HIV patients in asymptomatic infection, (b) DA increase does not modulate the availability of DA transporters and D2-receptors, (c) DA correlates inversely with CD4+ numbers in blood. These findings show activation of central DA systems without development of adaptive responses at DA synapses in asymptomatic HIV infection. It is probable that DA deterioration in advanced stages of HIV infection may derive from increased DA availability in early infection, resulting in DA neurotoxicity. Our findings provide a clue to the synergism between DA medication or drugs of abuse and HIV infection to exacerbate and accelerate HIV neuropsychiatric disease, a central issue in the neurobiology of HIV.
Scheller
C
C
Institute of Virology and Immunobiology, University of Würzburg, Versbacherstr. 7, 97078 Würzburg, Germany.
Arendt
G
G
Nolting
T
T
Antke
C
C
Sopper
S
S
Maschke
M
M
Obermann
M
M
Angerer
A
A
Husstedt
I W
IW
Meisner
F
F
Neuen-Jacob
E
E
Müller
H W
HW
Carey
P
P
Ter Meulen
V
V
Riederer
P
P
Koutsilieri
E
E
D015102:3,4-Dihydroxyphenylacetic Acid / Q000134:cerebrospinal fluid; D000328:Adult; D001549:Benzamides; D015704:CD4 Antigens / Q000378:metabolism; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005695:Galactosephosphates / Q000378:metabolism; D006678:HIV / Q000235:genetics; D015658:HIV Infections / Q000134:cerebrospinal fluid / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines; D009435:Synaptic Transmission / Q000502:physiology*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014326:Tropanes; D019562:Viral Load / Q000379:methods
D001549:Benzamides; C111835:CCL2 protein, human; D015704:CD4 Antigens; D018932:Chemokine CCL2; D005695:Galactosephosphates; D011759:Pyrrolidines; D014326:Tropanes; C097493:galactitol 3-phosphate; D015102:3,4-Dihydroxyphenylacetic Acid; C087552:2-carbomethoxy-8-(3-fluoropropyl)-3-(4-iodophenyl)tropane; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D004298:Dopamine; D006719:Homovanillic Acid
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