article published yes Gabriela Brailoiu author Elena Deliu author 37A40D7E-F248-11E8-B48F-1D18A9856A870000-0002-7370-5293 Jeffrey Barr author Linda Console Bram author Alexandra Ciuciu author Mary Abood author Ellen Unterwald author Eugen Brǎiloiu author GaNo department 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. Elsevier2017 eng 0376-8716 28623807 00040915230000210.1016/j.drugalcdep.2017.04.015 1787 - 14 Brailoiu G, Deliu E, Barr J, Console Bram L, Ciuciu A, Abood M, Unterwald E, Brǎiloiu E. 2017. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 178, 7–14. Brailoiu, G., Deliu, E., Barr, J., Console Bram, L., Ciuciu, A., Abood, M., … Brǎiloiu, E. (2017). HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. <i>Drug and Alcohol Dependence</i>. Elsevier. <a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">https://doi.org/10.1016/j.drugalcdep.2017.04.015</a> G. Brailoiu, E. Deliu, J. Barr, L. Console Bram, A. Ciuciu, M. Abood, E. Unterwald, E. Brǎiloiu, Drug and Alcohol Dependence 178 (2017) 7–14. Brailoiu, Gabriela, Elena Deliu, Jeffrey Barr, Linda Console Bram, Alexandra Ciuciu, Mary Abood, Ellen Unterwald, and Eugen Brǎiloiu. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” <i>Drug and Alcohol Dependence</i>. Elsevier, 2017. <a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">https://doi.org/10.1016/j.drugalcdep.2017.04.015</a>. 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> G. Brailoiu <i>et al.</i>, “HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens,” <i>Drug and Alcohol Dependence</i>, vol. 178. Elsevier, pp. 7–14, 2017. Brailoiu, Gabriela, et al. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” <i>Drug and Alcohol Dependence</i>, vol. 178, Elsevier, 2017, pp. 7–14, doi:<a href="https://doi.org/10.1016/j.drugalcdep.2017.04.015">10.1016/j.drugalcdep.2017.04.015</a>. 7142018-12-11T11:48:05Z2026-04-16T10:01:59Z