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Fruit Fly Study Finds Addiction-Linked Dopamine Mechanism Drives Natural Fatigue

Published in Nature Neuroscience, the work identifies D2 receptor desensitization as the switch that devalues repeated behavior in male flies.

Overview

  • Researchers at Boston Children's Hospital traced repetition-induced devaluation to β-arrestin–dependent desensitization of D2 receptors on copulation decision neurons.
  • Dopamine signaling via D2 receptors kept males engaged during mating, yet prior matings made the receptors less responsive and increased termination under stress.
  • Supplying extra dopamine did not restore persistence, indicating receptor resistance rather than reduced release.
  • Blocking local desensitization removed behavioral fatigue, with males persisting as if at a first mating.
  • Findings establish a mechanistic bridge between drug tolerance and everyday motivation loss in an insect model, with vertebrate relevance still untested.