HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens Brailoiu, Gabriela Deliu, Elena ; https://orcid.org/0000-0002-7370-5293 Barr, Jeffrey Console Bram, Linda Ciuciu, Alexandra Abood, Mary Unterwald, Ellen Brǎiloiu, Eugen Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients. Elsevier 2017 info:eu-repo/semantics/article doc-type:article article http://purl.org/coar/resource_type/c_2df8fbb1 https://research-explorer.ista.ac.at/record/714 Brailoiu G, Deliu E, Barr J, et al. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. <i>Drug and Alcohol Dependence</i>. 2017;178:7-14. doi:<a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">10.1016/j.drugalcdep.2017.04.015</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.drugalcdep.2017.04.015 info:eu-repo/semantics/altIdentifier/issn/0376-8716 info:eu-repo/semantics/altIdentifier/wos/000409152300002 info:eu-repo/semantics/altIdentifier/pmid/28623807 info:eu-repo/semantics/openAccess