Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers

Joan S. Hult papers

Dr. Joan S. Hult (1933- ) was a professor of kinesiology and sports history at the University of Maryland from 1968 until 1996. In her early years, particularly in her own college career, she was an all-around athlete. She received a B.S from Indiana University, a Masters in Education from the University of North Carolina at Greensboro, and a Ph.D from the University of Southern California. She coached the women's tennis team at Maryland until she resigned in protest. Hult was a strong supporter of the Title IX Gender Equality in Sports legislation and a member of the Association for Intercollegiate Athletics for Women (AIAW) board before the association merged with the NCAA. She has published many books and papers on the history of women in sports, the history of the Olympic Games, and the history of sports in general. After her retirement, Hult remained active in the sports history world. This collection spans Hult's career and includes correspondence, teaching materials from undergraduate and graduate courses, articles, newspaper clippings, brochures and publications, research notes, and writings by Hult -- all of which cover a range of sports history and women's history topics. The Hult papers are unprocessed, but preliminary inventories are available