PMID- 33538092
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20240214
IS  - 1369-1600 (Electronic)
IS  - 1355-6215 (Print)
IS  - 1355-6215 (Linking)
VI  - 26
IP  - 4
DP  - 2021 Jul
TI  - Tyramine synthesis, vesicular packaging, and the SNARE complex function 
      coordinately in astrocytes to regulate Drosophila alcohol sedation.
PG  - e13019
LID - 10.1111/adb.13019 [doi]
AB  - Identifying mechanisms underlying alcohol-related behaviors could provide 
      important insights regarding the etiology of alcohol use disorder. To date, most 
      genetic studies on alcohol-related behavior in model organisms have focused on 
      neurons, leaving the causal roles of glial mechanisms less comprehensively 
      investigated. Here, we report our studies on the role of Tyrosine decarboxylase 2 
      (Tdc2), which converts tyrosine to the catecholamine tyramine, in glial cells in 
      Drosophila alcohol sedation. Using genetic approaches that drove transgene 
      expression constitutively in all glia, constitutively in astrocytes and 
      conditionally in glia during adulthood, we found that knockdown and 
      overexpression of Tdc2, respectively, increased and decreased the sensitivity to 
      alcohol sedation in flies. Manipulation of the genes tyramine beta-hydroxylase and 
      tyrosine hydroxylase, which respectively synthesize octopamine and dopamine from 
      tyramine and tyrosine, had no discernable effect on alcohol sedation, suggesting 
      that Tdc2 affects alcohol sedation by regulating tyramine production. We also 
      found that knockdown of the vesicular monoamine transporter (VMAT) and disruption 
      of the SNARE complex in all glia or selectively in astrocytes increased 
      sensitivity to alcohol sedation and that both VMAT and the SNARE complex 
      functioned downstream of Tdc2. Our studies support a model in which the synthesis 
      of tyramine and vesicle-mediated release of tyramine from adult astrocytes 
      regulates alcohol sedation in Drosophila. Considering that tyramine is 
      functionally orthologous to norepinephrine in mammals, our results raise the 
      possibility that gliotransmitter synthesis release could be a conserved mechanism 
      influencing behavioral responses to alcohol as well as alcohol use disorder.
CI  - (c) 2021 Society for the Study of Addiction.
FAU - Lee, Kristen M
AU  - Lee KM
AUID- ORCID: 0000-0003-4527-6468
AD  - Neuroscience Graduate Program, Virginia Commonwealth University, Richmond, 
      Virginia, USA.
FAU - Talikoti, Ananya
AU  - Talikoti A
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      Richmond, Virginia, USA.
FAU - Shelton, Keith
AU  - Shelton K
AD  - Department of Pharmacology and Toxicology, Virginia Commonwealth University, 
      Richmond, Virginia, USA.
FAU - Grotewiel, Mike
AU  - Grotewiel M
AUID- ORCID: 0000-0001-7302-3252
AD  - Neuroscience Graduate Program, Virginia Commonwealth University, Richmond, 
      Virginia, USA.
AD  - Department of Human and Molecular Genetics, Virginia Commonwealth University, 
      Richmond, Virginia, USA.
AD  - Virginia Commonwealth University Alcohol Research Center, Virginia Commonwealth 
      University, Richmond, Virginia, USA.
LA  - eng
GR  - P40 OD018537/OD/NIH HHS/United States
GR  - F31 AA026500/AA/NIAAA NIH HHS/United States
GR  - R21 DA048242/DA/NIDA NIH HHS/United States
GR  - R21 DA042181/DA/NIDA NIH HHS/United States
GR  - P30 CA016059/CA/NCI NIH HHS/United States
GR  - R01 AA020634/AA/NIAAA NIH HHS/United States
GR  - P50 AA022537/AA/NIAAA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210203
PL  - United States
TA  - Addict Biol
JT  - Addiction biology
JID - 9604935
RN  - 0 (SNARE Proteins)
RN  - 0 (Vesicular Monoamine Transport Proteins)
RN  - 14O50WS8JD (Octopamine)
RN  - 3K9958V90M (Ethanol)
RN  - EC 1.- (Mixed Function Oxygenases)
RN  - EC 1.14.- (tyramine beta-hydroxylase)
RN  - EC 4.1.1.25 (Tyrosine Decarboxylase)
RN  - VTD58H1Z2X (Dopamine)
RN  - X8ZC7V0OX3 (Tyramine)
SB  - IM
MH  - Alcohol Drinking/*metabolism
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Cytoplasm/metabolism
MH  - Dopamine/metabolism
MH  - Drosophila/*metabolism
MH  - Ethanol/metabolism
MH  - Female
MH  - Mixed Function Oxygenases
MH  - Neurons/metabolism
MH  - Octopamine/metabolism
MH  - SNARE Proteins/*metabolism
MH  - Tyramine/*biosynthesis
MH  - Tyrosine Decarboxylase/metabolism
MH  - Vesicular Monoamine Transport Proteins/*metabolism
PMC - PMC8225576
MID - NIHMS1688888
OTO - NOTNLM
OT  - Drosophila
OT  - VMAT
OT  - alcohol
OT  - astrocytes
OT  - glia
OT  - tyramine
COIS- DISCLOSURE/CONFLICT OF INTEREST The authors declare no competing financial 
      interests.
EDAT- 2021/02/05 06:00
MHDA- 2021/12/15 06:00
PMCR- 2022/01/01
CRDT- 2021/02/04 05:58
PHST- 2021/01/08 00:00 [revised]
PHST- 2020/07/10 00:00 [received]
PHST- 2021/01/19 00:00 [accepted]
PHST- 2021/02/05 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/02/04 05:58 [entrez]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.1111/adb.13019 [doi]
PST - ppublish
SO  - Addict Biol. 2021 Jul;26(4):e13019. doi: 10.1111/adb.13019. Epub 2021 Feb 3.