A Review on HIV's Effects on Exploratory Activity, Motor Functions, and Learning in Animals

Infection with the human immunodeficiency virus (HIV) causes human neuropsycho-logical disorders, such as apathy and hypokinesia, as well as deficits in motor skills, selective attention, and learning. Based on findings from multiple studies, similar signs have been repro-duced in animal models following intracerebral injections of HIV-infected human monocytes or monocyte-derived macrophages, or exposure to gp120, Tat, or Nef. These include learning defi-cits in Morris, radial arm, and Barnes mazes; impairments in novel object place and shape recog-nition; motor coordination deficits on stationary and mobile beams; and hypoactivity. Relative to non-transgenic controls, deficits in most tests have also been reproduced in transgenic mice or rats expressing HIV-1 or related proteins. There is evidence that corticosterone contributes to these behavioral abnormalities, which may have implications for treating AIDS dementia com-plex, given its ability to exacerbate the neurotoxic effects of gp120 in tissue cultures. Possible mechanisms include corticosterone-induced worsening of lipid peroxidation, inhibition of aspar-tate uptake, increased calcium mobilization, and reduced ATP levels.