Neurotoxicity and dysfunction of dopaminergic systems associated with AIDSdementia

Infection with the human immunodefiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequent ly asymptomatic, some patients may develop signs of dopamine deficiency de novo, Accordingly, they are highly susceptible to drugs that act on dopamin ergic systems. Both neuroleptics and psychostimulants may exacerbate these symptoms. Experimental evidence suggests that viral proteins such as gp120 and Tat can cause toxicity to dopaminergic neurons, and this toxicity is sy nergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modul ate dopaminergic function, such as glutamate and opioids, may also modify t he susceptibility of the dopamine system to HIV. Therefore, a thorough unde rstanding of the mechanisms that lead to this selective neurotoxicity of do paminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.