Chronic methamphetamine exposure exerts few effects on the iTat mouse model of HIV, but blocks Tat expression-induced slowed reward retrieval.

Autor: Young JW; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States. Electronic address: jaredyoung@ucsd.edu., Kenton JA; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States., Milienne-Petiot M; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States., Deben D; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands., Achim C; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States., Geyer MA; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States., Perry W; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States., Grant IE; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; Research Service, VA San Diego Healthcare System, San Diego, CA, United States; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands; VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA, United States., Minassian A; Department of Psychiatry, University of California San Diego, La Jolla, CA, United States; VA Center of Excellence for Stress and Mental Health, Veterans Administration San Diego HealthCare System, 3350 La Jolla Village Drive, San Diego, CA, United States.
Jazyk: angličtina
Zdroj: Behavioural brain research [Behav Brain Res] 2023 Feb 02; Vol. 437, pp. 114109. Date of Electronic Publication: 2022 Sep 13.
DOI: 10.1016/j.bbr.2022.114109
Abstrakt: Human immunodeficiency virus (HIV) continues to infect millions worldwide, negatively impacting neurobehavioral function. Further understanding of the combined effects of HIV and methamphetamine use is crucial, as methamphetamine use is prevalent in people with HIV. The HIV-associated protein Tat may contribute to cognitive dysfunction, modeled preclinically in mice using doxycycline (DOX)-inducible Tat expression (iTat). Tat may exert its effects on cognitive function via disruption of the dopamine transporter, similar to the action of methamphetamine. Additionally, Tat and methamphetamine both decrease interneuron populations, including those expressing calbindin. It is important to understand the combined effects of Tat and methamphetamine in preclinical models of HIV infection. Here, we used iTat transgenic mice and a chronic binge regimen of methamphetamine exposure to determine their combined impact on reward learning and motivation. We also measured calbindin expression in behavior-relevant brain regions. Before induction with DOX, iTat mice exhibited no differences in behavior. Chronic methamphetamine exposure before Tat induction impaired initial reward learning but did not affect motivation. Furthermore, DOX-induced Tat expression did not alter behavior, but slowed latencies to retrieve rewards. This effect of Tat, however, was not observed in methamphetamine-treated mice, indicative of a potential protective effect. Finally, Tat expression was associated with an increase in calbindin-expressing cells in the VTA, while methamphetamine exposure did not alter calbindin numbers. These findings may indicate a protective role of methamphetamine in HIV neuropathology, which in turn may help in our understanding of why people with HIV use methamphetamine at disproportionately higher rates.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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