cART Exacerbates Cocaine-Induced Cortical Neuron Hyperactivity in Non-Transgenic but Not HIV-1 Transgenic Rats

Area of Science:

• Neuroscience
• Pharmacology
• Virology

Background:

• HIV-associated neurocognitive disorders (HAND) persist despite combination antiretroviral therapy (cART).
• Cocaine (COC) use and cART independently disrupt medial prefrontal cortex (mPFC) function.
• The combined neurotoxic impact of COC, HAND, and cART is a critical clinical concern.

Purpose of the Study:

• To investigate the effects of repeated cocaine (COC) exposure and/or combination antiretroviral therapy (cART) on medial prefrontal cortex (mPFC) pyramidal neuron activity.
• To compare these effects in HIV-1 transgenic (Tg) rats and non-transgenic (non-Tg) rats.

Main Methods:

• Utilized patch-clamp electrophysiology.
• Examined mPFC pyramidal neuron activity in HIV-1 Tg and non-Tg rats.
• Administered repeated exposure to COC and/or cART.

Main Results:

• In non-Tg rats, COC and cART independently increased neuronal firing, with a trend towards an additive hyperactive effect when combined.
• HIV-1 Tg rat neurons showed plateaued excitability; COC or cART did not further elevate firing.
• Neurons in both groups exhibited firing declines under intense depolarizing stimuli after treatment.

Conclusions:

• COC and cART additively disrupt mPFC function in non-Tg rats.
• Neuronal excitability mechanisms appear saturated in the HIV-1 Tg model.
• Findings highlight overlapping neurobiological impacts of cART and stimulant use in the context of HAND and COC use disorder.