title: Methamphetamine Exposure Combined with HIV-1 Disease or gp120 Expression: Comparison of Learning and Executive Functions in Humans and Mice.
abstract: Methamphetamine dependence is a common comorbid condition among people living with HIV, and may exacerbate HIV-associated neurocognitive disorders. Animal models of neuroAIDS suggest that the gp120 protein may also cause cognitive impairment. The present work evaluated the separate and combined effects of HIV/gp120 and methamphetamine on learning and executive functions in both humans and transgenic mice. Human participants were grouped by HIV serostatus (HIV+ or HIV-) and lifetime methamphetamine dependence (METH+ or METH-). A neurocognitive test battery included domain-specific assessments of learning and executive functions. Mice (gp120+ and gp120-) were exposed to either a methamphetamine binge (METH+) or saline (METH-), then tested in the attentional-set-shifting task to assess learning and executive functions. In humans, HIV status was associated with significant impairments in learning, but less so for executive functions. The frequency of learning impairments varied between groups, with the greatest impairment observed in the HIV+/METH+ group. In mice, gp120 expression was associated with impairments in learning but not reversal learning (executive component). The greatest proportion of mice that failed to complete the task was observed in the gp120+/METH+ group, suggesting greater learning impairments. Our cross-species study demonstrated that HIV in humans and gp120 in mice impaired learning, and that a history of methamphetamine exposure increased the susceptibility to HIV-associated neurocognitive deficits in both species. Finally, the similar pattern of results in both species suggest that the gp120 protein may contribute to HIV-associated learning deficits in humans.
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: James P
authors: JP
authors: Kesby
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Robert K
authors: RK
authors: Heaton
authors: 1] Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA [2] Research Service, VA San Diego Healthcare System, San Diego, CA, USA.
authors: Jared W
authors: JW
authors: Young
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Anya
authors: A
authors: Umlauf
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Steven P
authors: SP
authors: Woods
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Scott L
authors: SL
authors: Letendre
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Athina
authors: A
authors: Markou
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Igor
authors: I
authors: Grant
authors: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Svetlana
authors: S
authors: Semenova
mesh_terms: D000328:Adult; D000818:Animals; D001288:Attention / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003072:Cognition Disorders / Q000209:etiology*; D004305:Dose-Response Relationship, Drug; D056344:Executive Function / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism*; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007859:Learning Disabilities / Q000209:etiology*; D008694:Methamphetamine / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D009483:Neuropsychological Tests; D012193:Reversal Learning; D018709:Statistics, Nonparametric; D019966:Substance-Related Disorders / Q000150:complications*; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D015699:HIV Envelope Protein gp120; D008694:Methamphetamine
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