PMID- 28623807
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20181202
IS  - 1879-0046 (Electronic)
IS  - 0376-8716 (Print)
IS  - 0376-8716 (Linking)
VI  - 178
DP  - 2017 Sep 1
TI  - HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens.
PG  - 7-14
LID - S0376-8716(17)30256-9 [pii]
LID - 10.1016/j.drugalcdep.2017.04.015 [doi]
AB  - 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 Ca(2+) homeostasis of NAcc neurons. 
      RESULTS: We provide evidence that Tat triggers a Ca(2+) 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 
      (IP(3)) receptor-mediated Ca(2+) release from endoplasmic reticulum, followed by 
      Ca(2+) and Na(+) influx via transient receptor potential canonical channels. The 
      influx of cations depolarizes the membrane promoting additional Ca(2+) entry 
      through voltage-gated P/Q-type Ca(2+) 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 IP(3)-generating mechanisms are concomitantly initiated. When tested 
      here, cocaine produced a dose-dependent potentiation of the effect of Tat on 
      cytosolic Ca(2+). CONCLUSION: We describe for the first time a HIV-1 
      Tat-triggered Ca(2+) 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.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Brailoiu, G Cristina
AU  - Brailoiu GC
AD  - Department of Pharmaceutical Sciences, Jefferson College of Pharmacy, Thomas 
      Jefferson University, Philadelphia, PA 19107, USA.
FAU - Deliu, Elena
AU  - Deliu E
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA.
FAU - Barr, Jeffrey L
AU  - Barr JL
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA.
FAU - Console-Bram, Linda M
AU  - Console-Bram LM
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA.
FAU - Ciuciu, Alexandra M
AU  - Ciuciu AM
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA.
FAU - Abood, Mary E
AU  - Abood ME
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA; Department of Anatomy and Cell Biology, 
      Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
FAU - Unterwald, Ellen M
AU  - Unterwald EM
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA; Department of Pharmacology, Lewis Katz 
      School of Medicine at Temple University, Philadelphia, PA 19140, USA. Electronic 
      address: ellen.unterwald@temple.edu.
FAU - Brailoiu, Eugen
AU  - Brailoiu E
AD  - Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple 
      University, Philadelphia, PA 19140, USA. Electronic address: ebrailou@temple.edu.
LA  - eng
GR  - P30 DA013429/DA/NIDA NIH HHS/United States
GR  - R01 DA023204/DA/NIDA NIH HHS/United States
GR  - R01 DA035926/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20170608
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 9NEZ333N27 (Sodium)
RN  - I5Y540LHVR (Cocaine)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Calcium/metabolism
MH  - Cells, Cultured
MH  - Cocaine/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Drug Synergism
MH  - Female
MH  - Male
MH  - Neurons/metabolism/*physiology
MH  - Nucleus Accumbens/drug effects/*physiology
MH  - Rats
MH  - Receptors, Dopamine D1/*metabolism
MH  - Signal Transduction/physiology
MH  - Sodium/metabolism
MH  - tat Gene Products, Human Immunodeficiency Virus/pharmacology/*physiology
PMC - PMC5797705
MID - NIHMS937363
OTO - NOTNLM
OT  - Calcium imaging
OT  - Calcium influx
OT  - Depolarization
OT  - Intracellular calcium mobilization
OT  - Medium spiny neurons
OT  - TRPC
EDAT- 2017/06/18 06:00
MHDA- 2018/03/27 06:00
PMCR- 2018/09/01
CRDT- 2017/06/18 06:00
PHST- 2016/12/07 00:00 [received]
PHST- 2017/03/13 00:00 [revised]
PHST- 2017/04/17 00:00 [accepted]
PHST- 2017/06/18 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2017/06/18 06:00 [entrez]
PHST- 2018/09/01 00:00 [pmc-release]
AID - S0376-8716(17)30256-9 [pii]
AID - 10.1016/j.drugalcdep.2017.04.015 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2017 Sep 1;178:7-14. doi: 10.1016/j.drugalcdep.2017.04.015. 
      Epub 2017 Jun 8.