Welcome to the Designer Receptors Exclusively Activated by Designer Drugs DREADD wiki

For the most recent updates, available resources and protocols on DREADD technology please visit our blog

DREADDs are engineered G-protein coupled receptors which are activated by otherwise inert drug-like small molecules. In the example shown below, an evolved M3-muscarinic receptor is activated by the small molecule clozapine-N-oxide (CNO; see Armbruster et al, PNAS 2007 for details)

DREADDs are currently used by many labs to remotely and non-invasively control neuronal signaling

Helpful reviews on the technology:

Rogan and Roth, Pharmacol Rev 2011 Jun;63(2):291-315. Epub 2011 Mar 17.

Dong et al, Mol Biosystems 2010 Aug;6(8):1376-80. Epub 2010 Jun 7.


Gq-DREADD = hM3Dq = D-q ; clozapine-N-oxide activates Gq-mediated signaling. In neurons activation of hM3Dq induces burst firing

Gi-DREADD=hM4Di= D-i; clozapine-N-oxide induces Gi activation. In neurons, activation of hM4Di induces neuronal silencing

Gs-DREADD = Gs-D = D-s; clozapine-N-oxide induces Gs activation. In neurons this leads to an increase in cAMP.

Detailed Protocols for Creating DREADDs

Dong et al, Nature Protocols 2010;5(3):561-73. Epub 2010 Feb 25.

Listed below are various DREADD constructs currently available with links to VectorNTI files:

available in pcDNA3.0:

HA-tagged hM3D in pcDNA3: this is coupled to Gq and induces neuronal burst firing

HA-tagged hM4D in pcDNA3: this is coupled to Gi and induces neuronal silencing

HA-tagged Gs-DREADD in pcDNA3: this is coupled to Gs and elevates cAMP production

Available as FLEX-AAV Constructs using Synapsin-1 promotor (also known as DIO Vectors) (See Krashes et al, JCI 2011)
mCherry Fusion Proteins

hM3Dq-mCherry fusion protein construct Causes burst firing of neurons

hM4Di-mCherry fusion protein construct Silences neuronal firing

AAV-FLEX Constructs with Syanpsin-1 promotor; also contain IRES and either mCherry or mCitrine reporters: Validated in HEK-293 cells and neurons but not yet published.





How to obtain high-titer virus stocks: Each aliquot is ~$220 and no MTA needed. How to obtain:

  1. Please go to
  1. Fill out the order form for serotype 5, 2 or 8 virus. We find that AAV serotype 8 yields highest levels of neuronal expression and greatest spread of infection and is ideal for studies using DIO vectors. Serotypes 2 and 5 are best where localized expression is key.

Available in Lentiviral vectors



DREADDs targeted to neuronal subdomains (available for collaborative studies only):

Somato-dendritically-targeted DREADDs (hM4Di, hM3Dq)

Axonally-targeted DREADD (hM4Di, hM3Dq)

Glial-specific expression: AAV-GFAP minimal promotor available via UNC Vector core

Glial-specific Gs and Gq DREADDs (GsD and hM3Dq)

Mice currently available:

tet-HA-tagged hM3Dq mice:
tet-HA-tagged hM4Dq mice:

Adora2A-GsD mice:

The Jackson lab offers tet- HA-tagged hM4Di mice

The Jackson Laboratory offers tet-HA-tagged hM3Dq mice:

Adora2A-rM3Ds-mCherry mice:

Detailed protocol for HA-staining now available (see attachments below)

Detailed protocol for dissolving CNO now available (see attachments below)

Vector maps available for common vectors (see Attachments)

Last modified 8 months ago Last modified on 02/06/15 13:49:59

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