Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons

Mark A. Ungless, Vineeta Singh, Tara L. Crowder, Rami Yaka, Dorit Ron, Antonello Bonci*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

261 Scopus citations


Stress increases addictive behaviors and is a common cause of relapse. Corticotropin-releasing factor (CRF) plays a key role in the modulation of drug taking by stress. However, the mechanism by which CRF modulates neuronal activity in circuits involved in drug addiction is poorly understood. Here we show that CRF induces a potentiation of NMDAR (N-methyl-D-aspartate receptor)-mediated synaptic transmission in dopamine neurons of the ventral tegmental area (VTA). This effect involves CRF receptor 2 (CRF-R2) and activation of the phospholipase C (PLC)-protein kinase C (PKC) pathway. We also find that this potentiation requires CRF binding protein (CRF-BP). Accordingly, CRF-like peptides, which do not bind the CRF-BP with high affinity, do not potentiate NMDARs. These results provide evidence of the first specific roles for CRF-R2 and CRF-BP in the modulation of neuronal activity and suggest that NMDARs in the VTA may be a target for both drugs of abuse and stress.

Original languageAmerican English
Pages (from-to)401-407
Number of pages7
Issue number3
StatePublished - 31 Jul 2003

Bibliographical note

Funding Information:
We thank R.C. Malenka, R.O. Messing, A.J. Ravindranathan, J. Roeper, and Y. Shaham for many useful comments; the members of the Malenka lab and Bonci lab for helpful discussions; and L. Daitch for proofreading the manuscript. This work was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (A.B., T.L.C, M.A.U., R.Y., and D.R.) and by the National Institute of Neurological Disorders and Stroke (K23 NS42072) (V.S.).


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