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Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia

Department of Neurology, Microbiology and Immunology, University of Kentucky, Lexington, KY, USA; Kentucky Clinic L-445, Department of Neurology, Lexington, KY 40536—0284, USA; anath{at}pop.uky.edu

Carol Anderson

Melina Jones

Departments of Neurology, Microbiology and Immunology, University of Kentucky, Lexington, KY, USA

William Maragos

Departments of Neurology, Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA

Rosemarie Booze

Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA

Charles Mactutus

Tobacco Health Research Institute, University of Kentucky, Lexington, KY, USA

Jeanne Bell

Western General Hospital, Edinburgh, UK

Kurt F. Hauser

Mark Mattson

Anatomy and Neurobiology, University of Kentucky, Lexington, KY, USA

Infection with the human immunodefiency virus (HIV) selectively targets the basal ganglia resulting in loss of dopaminergic neurons. Although frequently asymptomatic, some patients may develop signs of dopamine deficiency de novo. Accordingly, they are highly susceptible to drugs that act on dopaminergic 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 synergistic with compounds such as methamphetamine and cocaine that also act on the dopaminergic system. In addition, other neurotransmitters that modulate dopaminergic function, such as glutamate and opioids, may also modify the susceptibility of the dopamine system to HIV. Therefore, a thorough understanding of the mechanisms that lead to this selective neurotoxicity of dopaminergic neurons would also likely lead to the development of therapeutic modalities for patients with HIV dementia.

Key Words: AIDS • basal ganglia • brain • cocaine • dementia • dopamine • HIV • methamphetamine • neuroleptics • opiates • ParkinsonÕs disease

Journal of Psychopharmacology, Vol. 14, No. 3, 222-227 (2000)
DOI: 10.1177/026988110001400305


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