PMID- 23658190
OWN - NLM
STAT- MEDLINE
DCOM- 20130806
LR  - 20230425
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 19
DP  - 2013 May 8
TI  - Small-molecule screen in adult Drosophila identifies VMAT as a regulator of 
      sleep.
PG  - 8534-40
LID - 10.1523/JNEUROSCI.0253-13.2013 [doi]
AB  - Sleep is an important physiological state, but its function and regulation remain 
      elusive. In Drosophila melanogaster, a useful model organism for studying sleep, 
      forward genetic screens have identified important sleep-modulating genes and 
      pathways; however, the results of such screens may be limited by developmental 
      abnormalities or lethality associated with mutation of certain genes. To 
      circumvent these limitations, we used a small-molecule screen to identify 
      sleep-modulating genes and pathways. We administered 1280 pharmacologically 
      active small molecules to adult flies and monitored their sleep. We found that 
      administration of reserpine, a small-molecule inhibitor of the vesicular 
      monoamine transporter (VMAT) that repackages monoamines into presynaptic 
      vesicles, resulted in an increase in sleep. Supporting the idea that VMAT is the 
      sleep-relevant target of reserpine, we found that VMAT-null mutants have an 
      increased sleep phenotype, as well as an increased arousal threshold and 
      resistance to the effects of reserpine. However, although the VMAT mutants are 
      consistently resistant to reserpine, other aspects of their sleep phenotype are 
      dependent on genetic background. These findings indicate that small-molecule 
      screens can be used effectively to identify sleep-modulating genes whose 
      phenotypes may be suppressed in traditional genetic screens. Mutations affecting 
      single monoamine pathways did not affect reserpine sensitivity, suggesting that 
      effects of VMAT/reserpine on sleep are mediated by multiple monoamines. Overall, 
      we identify VMAT as an important regulator of sleep in Drosophila and demonstrate 
      that small-molecule screens provide an effective approach to identify genes and 
      pathways that impact adult Drosophila behavior.
FAU - Nall, Aleksandra H
AU  - Nall AH
AD  - Cell and Molecular Biology Program and Department of Neuroscience, Howard Hughes 
      Medical Institute, Perelman School of Medicine, University of Pennsylvania, 
      Philadelphia, Pennsylvania 19104, USA.
FAU - Sehgal, Amita
AU  - Sehgal A
LA  - eng
GR  - T32 HL007953/HL/NHLBI NIH HHS/United States
GR  - 5 T32 HL 7953-12/HL/NHLBI NIH HHS/United States
GR  - 5-PO1-AG-017628/AG/NIA NIH HHS/United States
GR  - P01 AG017628/AG/NIA NIH HHS/United States
GR  - HHMI_/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Drosophila Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vesicular Monoamine Transport Proteins)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Genetically Modified
MH  - Antipsychotic Agents/pharmacology
MH  - Arousal/drug effects/genetics
MH  - Behavior, Animal/drug effects/physiology
MH  - Biogenic Monoamines/metabolism
MH  - Drosophila
MH  - Drosophila Proteins/genetics
MH  - Female
MH  - Genetic Testing
MH  - Mutation
MH  - Phenotype
MH  - RNA, Messenger/metabolism
MH  - Reaction Time/drug effects/genetics
MH  - Sleep/drug effects/*genetics
MH  - Sleep Deprivation
MH  - Vesicular Monoamine Transport Proteins/genetics/*metabolism
PMC - PMC3677510
MID - NIHMS477099
OID - NLM: HHMIMS477099
EDAT- 2013/05/10 06:00
MHDA- 2013/08/07 06:00
PMCR- 2013/11/08
CRDT- 2013/05/10 06:00
PHST- 2013/05/10 06:00 [entrez]
PHST- 2013/05/10 06:00 [pubmed]
PHST- 2013/08/07 06:00 [medline]
PHST- 2013/11/08 00:00 [pmc-release]
AID - 33/19/8534 [pii]
AID - 0253-13 [pii]
AID - 10.1523/JNEUROSCI.0253-13.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 May 8;33(19):8534-40. doi: 10.1523/JNEUROSCI.0253-13.2013.