HIV-1 proteins dysregulate motivational processes and dopamine circuitry

Sci Rep. 2018 May 18;8(1):7869. doi: 10.1038/s41598-018-25109-0.

Abstract

Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choice Behavior / drug effects
  • Cocaine / pharmacology
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism*
  • HIV Infections / metabolism
  • HIV Infections / pathology
  • HIV-1 / metabolism*
  • Human Immunodeficiency Virus Proteins / metabolism*
  • Neostriatum / drug effects
  • Neostriatum / metabolism
  • Rats
  • Rats, Inbred F344
  • Rats, Transgenic
  • Reinforcement, Psychology
  • Self Administration
  • Sucrose / pharmacology

Substances

  • Human Immunodeficiency Virus Proteins
  • Sucrose
  • Cocaine
  • Dopamine