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

J Neurovirol. 2019 Aug;25(4):540-550. doi: 10.1007/s13365-019-00754-x. Epub 2019 May 17.

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.

Keywords: Dopamine; Fast-scan cyclic voltammetry; HIV-1; Histamine immunohistochemistry; Nucleus accumbens; Serotonin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apathy
  • Depression / metabolism
  • Depression / psychology
  • Depression / virology
  • Dopamine / metabolism*
  • Female
  • HIV Infections / metabolism
  • HIV Infections / psychology
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • Histamine / metabolism*
  • Hypothalamus / metabolism*
  • Hypothalamus / virology
  • Male
  • Models, Biological
  • Nucleus Accumbens / metabolism*
  • Nucleus Accumbens / virology
  • Prefrontal Cortex / metabolism*
  • Prefrontal Cortex / virology
  • Rats
  • Rats, Inbred F344
  • Rats, Transgenic
  • Serotonin / metabolism*
  • Sex Factors
  • Synaptic Transmission
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics

Substances

  • Viral Proteins
  • Serotonin
  • Histamine
  • Dopamine