HIV-1 Tat and morphine interactions dynamically shift striatal monoamine levels and exploratory behaviors over time

Area of Science:

• Neuroscience
• Virology
• Pharmacology

Background:

• Despite combination anti-retroviral therapy (cART), HIV-associated neurocognitive disorders (HAND) persist in nearly half of treated individuals.
• Opioid use disorder can exacerbate HAND, particularly affecting the basal ganglia, which are vulnerable to HIV-1 and opioid co-exposure.
• While HIV is known to disrupt dopaminergic neurotransmission, the effects of co-exposure to opioids on striatal neurotransmitters and behavior remain unclear.

Purpose of the Study:

• To investigate how co-exposure to HIV-1 Tat protein and morphine affects monoamine levels and neurotransmitter metabolites in the striatum.
• To determine the impact of Tat and/or morphine exposure on motor, anxiety-like, novelty-seeking, exploratory, and social behaviors in transgenic mice.
• To elucidate the neurochemical underpinnings of behavioral changes associated with HIV-1 infection and opioid use.

Main Methods:

• Transgenic mice were exposed to HIV-1 Tat protein and/or morphine for 2 weeks and 2 months.
• Assayed motor, anxiety-like, novelty-seeking, exploratory, and social behaviors.
• Quantified levels of monoamines (dopamine, norepinephrine) and their metabolites (DOPAC, HVA, 5-HIAA) in the striatum.
• Evaluated tyrosine hydroxylase-positive neuron counts in the mesencephalon.

Main Results:

• Morphine decreased dopamine but increased norepinephrine, DOPAC, HVA, and 5-HIAA, correlating with increased locomotor activity.
• Combined Tat and morphine exposure altered dopamine, DOPAC, and HVA concentrations distinctively based on duration and specific neurotransmitter/metabolite.
• Tat exposure selectively increased latency to interact with novel conspecifics, while morphine increased exploration of novel environments; locomotor activity was affected by Tat and morphine interaction over time.

Conclusions:

• HIV-1 Tat and morphine exert distinct and interactive effects on striatal monoamine neurochemistry and behavior.
• These findings provide novel insights into the neurobiological mechanisms underlying HAND and the behavioral consequences of co-morbid HIV and opioid use.
• The study highlights context-dependent behavioral alterations and time-dependent interactions between HIV-1 Tat and morphine on motor function.