--- res: bibo_abstract: - 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.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Gabriela foaf_name: Brailoiu, Gabriela foaf_surname: Brailoiu - foaf_Person: foaf_givenName: Elena foaf_name: Deliu, Elena foaf_surname: Deliu foaf_workInfoHomepage: http://www.librecat.org/personId=37A40D7E-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-7370-5293 - foaf_Person: foaf_givenName: Jeffrey foaf_name: Barr, Jeffrey foaf_surname: Barr - foaf_Person: foaf_givenName: Linda foaf_name: Console Bram, Linda foaf_surname: Console Bram - foaf_Person: foaf_givenName: Alexandra foaf_name: Ciuciu, Alexandra foaf_surname: Ciuciu - foaf_Person: foaf_givenName: Mary foaf_name: Abood, Mary foaf_surname: Abood - foaf_Person: foaf_givenName: Ellen foaf_name: Unterwald, Ellen foaf_surname: Unterwald - foaf_Person: foaf_givenName: Eugen foaf_name: Brǎiloiu, Eugen foaf_surname: Brǎiloiu bibo_doi: 10.1016/j.drugalcdep.2017.04.015 bibo_volume: 178 dct_date: 2017^xs_gYear dct_isPartOf: - http://id.crossref.org/issn/03768716 dct_language: eng dct_publisher: Elsevier@ dct_title: HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens@ fabio_hasPubmedId: '28623807' ...