Disrupted Decision-Making: EcoHIV Inoculation in Cocaine Dependent Rats

Area of Science:

• Neuroscience
• Infectious Diseases
• Addiction Research

Background:

• Chronic cocaine use and HIV-1 infection independently cause neuroadaptations in the frontal-striatal circuit.
• The combined effects of HIV-1 infection and chronic drug use on this circuit remain understudied.

Purpose of the Study:

• To investigate the impact of HIV-1 infection on decision-making and frontal-striatal circuit function in the context of prior drug use experience.
• To establish a valid animal model for studying HIV-1 and chronic drug use interactions.

Main Methods:

• Utilized a pretest-posttest experimental design in rats with prior cocaine or sucrose self-administration experience.
• Assessed decision-making through preference judgment following inoculation with chimeric HIV (EcoHIV) or saline.
• Examined structural alterations in the frontal-striatal circuit, specifically synaptodendritic changes in medial prefrontal cortex neurons.

Main Results:

• Rats showed a preference for cocaine (males) or sucrose (females) during pretest.
• HIV-1 (EcoHIV) inoculation, but not saline, disrupted decision-making 3 days and 6 weeks post-inoculation, irrespective of biological sex.
• Significant synaptodendritic alterations were observed in medial prefrontal cortex pyramidal neurons, indicating structural damage.

Conclusions:

• HIV-1 infection significantly disrupts decision-making and induces structural neuroadaptations in the frontal-striatal circuit.
• The EcoHIV rat model is suitable for studying the neurological consequences of HIV-1 infection in individuals with a history of drug use.
• Findings highlight the vulnerability of the frontal-striatal circuit to HIV-1 infection, particularly following chronic drug exposure.