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Related Experiment Video

Updated: Jan 28, 2026

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Modulating Dopamine Signaling and Behavior with Chemogenetics: Concepts, Progress, and Challenges.

Annika Højrup Runegaard1, Ciarán Martin Fitzpatrick1, David Paul Drucker Woldbye1

  • 1Molecular Neuropharmacology and Genetics Laboratory, Department of Neuroscience (A.H.R., D.P.D.W., A.T.S., U.G.) and Department of Drug Design and Pharmacology (C.M.F., J.T.A.), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Pharmacological Reviews
|March 1, 2019
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Summary

Chemogenetics, using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), offers powerful control over dopamine (DA) signaling. This technique advances understanding of DA system functions and related behaviors, despite some ligand challenges.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Dopamine (DA) is a key neurotransmitter regulating motor control, motivation, and endocrine functions.
  • DA system dysregulation is implicated in Parkinson's disease, schizophrenia, and addiction.
  • The complexity of the DA system hinders understanding of its pathological mechanisms.

Purpose of the Study:

  • To review the application of chemogenetics in studying the dopamine system.
  • To highlight how chemogenetics has advanced the understanding of DA signaling and behavior.
  • To discuss the challenges and potential of chemogenetic tools in neuroscience research.

Main Methods:

  • Utilizing Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) for targeted neuronal control.
  • Employing chemogenetics to achieve pharmacological remote control of neuronal activity.
  • Reviewing recent studies that applied chemogenetics to the dopamine system.

Main Results:

  • Chemogenetics has significantly advanced the functional study of the DA system.
  • This technique provides novel insights into DA signaling pathways and associated behaviors.
  • Identified challenges include ligand metabolism, such as clozapine N-oxide (CNO) conversion to clozapine.

Conclusions:

  • Chemogenetics is an exceptional tool for studying neuronal function, particularly within the DA system.
  • Despite challenges, the chemogenetic toolbox holds immense potential for future research.
  • Continued refinement of chemogenetic techniques will further elucidate DA signaling mechanisms in health and disease.