Disrupted Decision-Making: EcoHIV Inoculation in Cocaine Dependent Rats

Int J Mol Sci. 2022 Aug 13;23(16):9100. doi: 10.3390/ijms23169100.

Abstract

Independently, chronic cocaine use and HIV-1 viral protein exposure induce neuroadaptations in the frontal-striatal circuit as evidenced by both clinical and preclinical studies; how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use, however, has remained elusive. After establishing experience with both sucrose and cocaine self-administration, a pretest-posttest experimental design was utilized to evaluate preference judgment, a simple form of decision-making dependent upon the integrity of frontal-striatal circuit function. During the pretest assessment, male rats exhibited a clear preference for cocaine, whereas female animals preferred sucrose. Two posttest evaluations (3 days and 6 weeks post inoculation) revealed that, independent of biological sex, inoculation with chimeric HIV (EcoHIV), but not saline, disrupted decision-making. Prominent structural alterations in the frontal-striatal circuit were evidenced by synaptodendritic alterations in pyramidal neurons in the medial prefrontal cortex. Thus, the EcoHIV rat affords a valid animal model to critically investigate how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use.

Keywords: dendritic spines; human immunodeficiency virus type 1; prefrontal cortex; pyramidal neurons; self-administration.

MeSH terms

  • Animals
  • Cocaine* / pharmacology
  • Cocaine-Related Disorders* / metabolism
  • Female
  • Male
  • Prefrontal Cortex / metabolism
  • Pyramidal Cells
  • Rats
  • Sucrose / metabolism

Substances

  • Sucrose
  • Cocaine