Disrupted Decision-Making: EcoHIV Inoculation Following a History of Cocaine Use

Abstract

Independently, chronic cocaine use and HIV-1 viral protein exposure induce neuroadaptations in the frontal-striatal circuit; how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use, however, has remained elusive. After establishing a history of 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 frontal-striatal circuit dysfunction were evidenced by synaptodendritic alterations in pyramidal neurons in the medial prefrontal cortex. Thus, the EcoHIV rat affords a biological system to model how the frontal-striatal circuit responds to HIV-1 infection following chronic drug use.