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Brain Structure and Function

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21.06.2018 | Short Communication

Region-specific changes in markers of neuroplasticity revealed in HIV-1 transgenic rats by low-dose methamphetamine

verfasst von: Michael Ohene-Nyako, Amanda L. Persons, T. Celeste Napier

Erschienen in: Brain Structure and Function | Ausgabe 7/2018

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Abstract

Methamphetamine abuse co-occurring with HIV infection presents neuropathology in brain regions that mediate reward and motivation. A neuronal signaling cascade altered acutely by meth and some HIV-1 proteins is the mitogen-activated protein kinase (MAPK) pathway. It remains unknown if chronic co-exposure to meth and HIV-1 proteins converge on MAPK in vivo. To make this determination, we studied young adult Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats that self-administered meth (0.02–0.04 mg/kg/0.05 ml iv infusion, 2 h/day for 21 days) and their saline-yoked controls. One day following the operant task, rats were killed. Brain regions involved in reward-motivation [i.e., nucleus accumbens (NA) and ventral pallidum (VP)], were assayed for a MAPK cascade protein, extracellular signal-regulated kinase (ERK), and a downstream transcription factor, ΔFosB. In the NA, activated (phosphorylated; p) ERK-to-ERK ratio (pERK/ERK) was increased in meth-exposed Tg rats versus saline Tg controls, and versus meth non-Tg rats. ΔFosB was increased in meth Tg rats versus saline and meth non-Tg rats. Assessment of two targets of ΔFosB-regulated transcription revealed (1) increased dopamine D1 receptor (D1R) immunoreactivity in the NA shell of Tg-meth rats versus saline Tg controls, but (2) no changes in the AMPA receptor subunit, GluA2. No changes related to genotype or meth occurred for ERK, ΔFosB or D1R protein in the VP. Results reveal a region-specific activation of ERK, and increases in ΔFosB and D1R expression induced by HIV-1 proteins and meth. Such effects may contribute to the neuronal and behavioral pathology associated with meth/HIV comorbidity.

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Titel: Region-specific changes in markers of neuroplasticity revealed in HIV-1 transgenic rats by low-dose methamphetamine
verfasst von: Michael Ohene-Nyako
Amanda L. Persons
T. Celeste Napier
Publikationsdatum: 21.06.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Brain Structure and Function / Ausgabe 7/2018
Print ISSN: 1863-2653
Elektronische ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-018-1701-6

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Region-specific changes in markers of neuroplasticity revealed in HIV-1 transgenic rats by low-dose methamphetamine

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