Resolving Behavioral Output via Chemogenetic Designer Receptors Exclusively Activated by Designer Drugs.
Designer receptors exclusively activated by designer drugs (DREADDs) have proven to be highly effective neuromodulatory tools for the investigation of neural circuits underlying behavioral outputs. They exhibit a number of advantages: they rely on cell-specific manipulations through canonical intracellular signaling pathways, they are easy and cost-effective to implement in a laboratory setting, and they are easily scalable for single-region or full-brain manipulations. On the other hand, DREADDs rely on ligand-G-protein-coupled receptor interactions, leading to coarse temporal dynamics. In this review we will provide a brief overview of DREADDs, their implementation, and the advantages and disadvantages of their use in animal systems. We also will provide numerous examples of their use across a broad variety of biomedical research fields.
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, and Brown University-National Institutes of Health Graduate Partnerships Program, Providence, Rhode Island 02912.
C Joseph
CJ
Burnett
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, and michael.krashes@nih.gov.
Michael J
MJ
Krashes
D000818:Animals; D001519:Behavior / Q000187:drug effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D015198:Designer Drugs / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D058990:Molecular Targeted Therapy; D009474:Neurons / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*
D015198:Designer Drugs; D043562:Receptors, G-Protein-Coupled
DREADD; behavior; cell-type specificity; chemogenetics