Molecular mechanisms of dopaminergic transmission in NeuroHIV

In this chapter, we discuss recent advances in understanding molecular mechanisms of dopaminergic transmission in NeuroHIV that potentially contributes to HIV-associated neurocognitive disorders (HANDs), particularly the neurophysiological changes in dopaminergic neurotransmission induced by HIV-1 transactivator of transcription (Tat) protein and substances of abuse. This chapter covers recent research outcomes from integrated computational modeling and experimental validation including in vitro and in vivo studies on the HIV-1 Tat protein interacting with monoamine transporters, as well as behavioral assessment in an inducible Tat transgenic mouse model in response to substances of abuse. We also discuss novel small molecules that show a potential for therapeutic intervention for Tat-induced dysregulation of dopamine transmission in the context of NeuroHIV.