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| Publication Abstract Display | | Type: Poster | | Title: A tale of mice and men: Translational cross-species assessment of inhibitory deficits in HIV and comorbid methamphetamine dependence using a novel human open-field paradigm. | | Authors: Henry BL, Minassian A, Geyer M, Perry W | | Date: 05-29-2012 | | Abstract:Inhibition, the process of withholding or attenuating an action or thought, is of central importance in the regulation of behavior and the ability to function in daily life. Deficits in inhibition are key features of both HIV and methamphetamine (METH) dependence and play a critical role in high-risk behaviors associated with drug use and disease transmission. Although HIV infection and METH exposure are both associated with cognitive dysfunction and neurotoxicity, the combined effects of these factors have not been examined comprehensively. While various domains of inhibition such as hyperactivity, novelty-seeking, and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar measures have not been applied in human subjects with neurological infections. Our group recently established a human open-field paradigm (Human Behavior Pattern Monitor: hBPM), where motor activity and behavior are quantified in a room containing furniture and engaging novel objects, a task directly based on models of rodent exploration. This project assessed inhibition in human participants with HIV infection and METH dependence as compared to a mouse model of HIV, gp120 transgenic mice exposed to chronic METH treatment. We hypothesized that the combined effects of HIV infection/gp120 expression and METH exposure in both species would induce greater inhibitory deficits in human/rodent open-field tests than either factor alone. Human subjects with comorbid HIV infection and METH dependence exhibited the greatest motor activity during the first several minutes in the hBPM relative to comparison groups, with a trend towards elevated multiple object interactions. Expression of the gp120 protein did not significantly impact locomotion in mouse open-field, but chronic METH administration increased novelty-seeking, including time spent with a novel object. These studies demonstrate the utility of cross-species paradigms that can be used to elucidate HIV neuropathology and assess inhibitory dysfunction associated with comorbid substance use. |
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