title: Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice.
abstract: Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e. similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: James P
authors.initials: JP
authors.lastname: Kesby
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA.
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
authors.affiliation: Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, M/C 0603, La Jolla, CA 92093, USA. Electronic address: ssemenova@ucsd.edu.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Semenova
mesh_terms: D000221:Adaptation, Ocular / Q000187:drug effects / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011930:Reaction Time / Q000187:drug effects; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D015699:HIV Envelope Protein gp120; D008694:Methamphetamine
keywords: Behavior; Recognition memory; Spatial learning; Transgenic