Selective monoaminergic and histaminergic circuit dysregulation following long-term HIV-1 protein exposure

Abstract

Between 30 and 60% of HIV-seropositive individuals develop symptoms of clinical depression and/or apathy. Dopamine and serotonin are associated with motivational alterations; however, histamine is less well studied. In the present study, we used fast-scan cyclic voltammetry in HIV-1 transgenic (Tg) rats to simultaneously analyze the kinetics of nucleus accumbens dopamine (DA), prefrontal cortical serotonin (5-HT), and hypothalamic histamine (HA). For voltammetry, subjects were 15 HIV-1 Tg (7 male, 8 female) and 20 F344/N (11 male, 9 female) adult rats. Both serotonergic and dopaminergic release and reuptake kinetics were decreased in HIV-1 Tg animals relative to controls. In contrast, rates of histamine release and reuptake increased in HIV-1 Tg rats. Additionally, we used immunohistochemical (IHC) methods to identify histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus. For IHC, subjects were 9 HIV-1 Tg (5 male, 4 female) and 9 F344/N (5 male, 4 female) adult rats. Although the total number of TMN histaminergic cells did not differ between HIV-1 Tg rats and F344/N controls, a significant sex effect was found, with females having an increased number of histaminergic neurons, relative to males. Collectively, these findings illustrate neurochemical alterations that potentially underlie or exacerbate the pathogenesis of clinical depression and/or apathy in HIV-1.

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Acknowledgments

The authors acknowledge and thank Dr. Michael Cranston and Dr. Hailong Li for their assistance with this project.

Funding

This research was supported by the National Institute of Health Grants NS100624, DA013137, HD043680, MH106392 & by a National Institute of Health T32 Training Grant 5T32GM081740.

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Correspondence to Rosemarie M. Booze.

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This experiment was conducted in accordance with the recommendations of the National Institute of Health’s Guide for the Care and Use of Laboratory Animals. Research protocols used were approved by the University of South Carolina Institutional Animal Care and Use Committee (assurance number: D16-00028). Additionally, the authors report no conflicts of interest or competing financial interests.

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Denton, A.R., Samaranayake, S.A., Kirchner, K.N. et al. Selective monoaminergic and histaminergic circuit dysregulation following long-term HIV-1 protein exposure. J. Neurovirol. 25, 540–550 (2019). https://doi.org/10.1007/s13365-019-00754-x

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Keywords

  • HIV-1
  • Nucleus accumbens
  • Fast-scan cyclic voltammetry
  • Dopamine
  • Serotonin
  • Histamine immunohistochemistry