Dopamine systems in human immunodeficiency virus-associated dementia.
OBJECTIVE
To provide an update of the neurobiologic basis of human immunodeficiency virus (HIV)-associated dementia (HAD), with emphasis on the relationship between dopamine (DA) system dysfunction and behavioral manifestations.


BACKGROUND
HIV has a propensity to invade subcortical central nervous system areas, particularly the basal ganglia. Indeed, the core symptoms of HAD are similar to those seen in patients with frontal-striatal dysfunction, the "subcortical dementias" (e.g., Parkinson disease, Huntington disease, progressive supranuclear palsy).


RESULTS
Damage to DA neurons appears to occur in early stages of the disease. Patients with HIV have decreased levels of cerebrospinal fluid DA, and patients with HAD have a reduction of the DA metabolite homovanillic acid but a relative preservation of other neurotransmitters, suggesting a loss of DA neurons. Neuropathologic examinations have shown neuronal loss of the globus pallidus, which is less severe in the neocortex. Furthermore, extrapyramidal signs and marked hypersensitivity to DA antagonists (e.g., neuroleptics) have a propensity to develop in patients with acquired immunodeficiency syndrome.


CONCLUSIONS
Neurobiologic investigations suggest that DA system dysfunction plays a critical role in the clinical manifestation of HIV infection, especially HAD. The causes of the vulnerability of this system to the infection are unknown. Understanding this mechanism is important to develop neuroprotective agents in the treatment of HAD and to design new therapies for HAD-related psychiatric symptoms.
Lopez
O L
OL
Department of Neurology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Smith
G
G
Meltzer
C C
CC
Becker
J T
JT
D015526:AIDS Dementia Complex / Q000175:diagnosis / Q000503:physiopathology*; D001931:Brain Mapping; D003342:Corpus Striatum / Q000503:physiopathology; D004298:Dopamine / Q000502:physiology*; D005625:Frontal Lobe / Q000503:physiopathology; D005917:Globus Pallidus / Q000503:physiopathology; D006801:Humans; D009474:Neurons / Q000502:physiology; D009483:Neuropsychological Tests; D010302:Parkinson Disease, Secondary / Q000175:diagnosis / Q000503:physiopathology
D004298:Dopamine