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Related Experiment Video

Updated: Jun 28, 2026

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area
09:54

Comprehensive Profiling of Dopamine Regulation in Substantia Nigra and Ventral Tegmental Area

Published on: August 10, 2012

Altered striatal dopamine regulation in Adgrl3 knockout mice.

Nicole A Perry-Hauser1,2,3,4, Arturo Torres-Herraez1,2,3, Siham Boumhaouad1,2,3,5,6

  • 1Department of Psychiatry, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|June 26, 2026
PubMed
Summary

The adhesion G protein-coupled receptor 3 (ADGRL3) influences dopamine release in the striatum. Loss of ADGRL3 alters dopamine signaling, impacting reward processing and behavior, potentially explaining links to ADHD.

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Last Updated: Jun 28, 2026

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Dopamine signaling is crucial for movement, learning, and reward, with dysregulation linked to ADHD and substance use disorder.
  • ADGRL3, a brain-enriched adhesion G protein-coupled receptor, is genetically associated with these neuropsychiatric conditions.
  • Previous studies show Adgrl3 knockout mice exhibit altered dopaminergic markers and behaviors, but the precise impact on dopamine dynamics is unclear.

Purpose of the Study:

  • To investigate the role of ADGRL3 in regulating striatal dopamine release and dynamics.
  • To characterize dopamine release in Adgrl3 knockout mice using both ex vivo and in vivo methods.

Main Methods:

  • Fast-scan cyclic voltammetry in acute brain slices to measure electrically evoked dopamine release.
  • In vivo fiber photometry with the dLight1.2 sensor during an operant fixed interval task.
  • Amphetamine challenge experiments to assess dopamine release capacity.

Main Results:

  • Adgrl3 knockout mice showed increased electrically evoked dopamine release in dorsal and ventral striatum ex vivo.
  • In vivo, Adgrl3 knockout mice exhibited reduced cue-induced dopamine signals in the ventral striatum during a task.
  • Behaviorally, knockout mice displayed longer latencies for reward acquisition, suggesting impaired cue-guided responses.

Conclusions:

  • ADGRL3 plays a significant role in regulating striatal dopamine release.
  • The findings suggest ADGRL3 loss impacts dopamine dynamics, potentially contributing to ADHD-like behavioral deficits.
  • Further research is needed to understand how ADGRL3 loss affects the spatial organization of dopaminergic terminals.