Dopamine systems in human immunodeficiency virus-associated dementia

Objective: To provide an update of the neurobiologic basis of human immunod eficiency virus (HIV)-associated dementia (HAD), with emphasis on the relat ionship between dopamine (DA) system dysfunction and behavioral manifestati ons. 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 dysfunctio n, the "subcortical dementias" (e.g., Parkinson disease, Huntington disease , progressive supranuclear palsy). Findings: Damage to DA neurons appears t o occur in early stages of the disease. Patients with HIV have decreased le vels of cerebrospinal fluid DA, and patients with HAD have a reduction of t he DA metabolite homovanillic acid but a relative preservation of other neu rotransmitters, suggesting a loss of DA. neurons. Neuropathologic examinati ons have shown neuronal loss of the globus pallidus, which is less severe i n the neocortex. Furthermore, extrapyramidal signs and marked hypersensitiv ity to DA antagonists (e.g., neuroleptics) have a propensity to develop in patients with acquired immunodeficiency syndrome. Conclusions: Neurobiologi c investigations suggest that DA system dysfunction plays a critical role i n the clinical manifestation of HIV infection, especially HAD. The causes o f the vulnerability of this system to the infection are unknown. Understand ing this mechanism is important to develop neuroprotective agents in the tr eatment of HAD and to design new therapies for HAD-related psychiatric symp toms.