Locomotor activity is regulated by D2-like receptors in Drosophila: An anatomic and functional analysis

Isabelle Draper, Peri T. Kurshan, Edward McBride, F. Rob Jackson, Alan S. Kopin

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

In mammals, dopamine 2-like receptors are expressed in distinct pathways within the central nervous system, as well as in peripheral tissues. Selected neuronal D2-like receptors play a critical role in modulating locomotor activity and, as such, represent an important therapeutic target (e.g. in Parkinson's disease). Previous studies have established that proteins required for dopamine (DA) neurotransmission are highly conserved between mammals and the fruit fly Drosophila melanogaster. These include a fly dopamine 2-like receptor (DD2R; Hearn et al. PNAS 2002 99(22):14554) that has structural and pharmacologic similarity to the human D2-like (D2R). In the current study, we define the spatial expression pattern of DD2R, and functionally characterize flies with reduced DD2 receptor levels. We show that DD2R is expressed in the larval and adult nervous systems, in cell groups that include the Ap-let cohort of peptidergic neurons, as well as in peripheral tissues including the gut and Malpighian tubules. To examine DD2R function in vivo, we generated RNA-interference (RNAi) flies with reduced DD2R expression. Behavioral analysis revealed that these flies show significantly decreased locomotor activity, similar to the phenotype observed in mammals with reduced D2R expression. The fly RNAi phenotype can be rescued by administration of the DD2R synthetic agonist bromocriptine, indicating specificity for the RNAi effect These results suggest Drosophila as a useful system for future studies aimed at identifying modifiers of dopaminergk signaling/locomotor function.

Original languageEnglish (US)
Pages (from-to)378-393
Number of pages16
JournalDevelopmental Neurobiology
Volume67
Issue number3
DOIs
StatePublished - Feb 15 2007
Externally publishedYes

Fingerprint

Locomotion
Diptera
Drosophila
RNA Interference
Mammals
Dopamine
Malpighian Tubules
Phenotype
Bromocriptine
Drosophila melanogaster
Synaptic Transmission
Nervous System
Parkinson Disease
Fruit
Central Nervous System
Neurons
Proteins

Keywords

  • D2-like receptor
  • Dopamine
  • Drosophila
  • Locomotor activity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Locomotor activity is regulated by D2-like receptors in Drosophila : An anatomic and functional analysis. / Draper, Isabelle; Kurshan, Peri T.; McBride, Edward; Jackson, F. Rob; Kopin, Alan S.

In: Developmental Neurobiology, Vol. 67, No. 3, 15.02.2007, p. 378-393.

Research output: Contribution to journalArticle

Draper, Isabelle ; Kurshan, Peri T. ; McBride, Edward ; Jackson, F. Rob ; Kopin, Alan S. / Locomotor activity is regulated by D2-like receptors in Drosophila : An anatomic and functional analysis. In: Developmental Neurobiology. 2007 ; Vol. 67, No. 3. pp. 378-393.
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