PMID- 12895416 OWN - NLM STAT- MEDLINE DCOM- 20030902 LR - 20220309 IS - 0896-6273 (Print) IS - 0896-6273 (Linking) VI - 39 IP - 3 DP - 2003 Jul 31 TI - Corticotropin-releasing factor requires CRF binding protein to potentiate NMDA receptors via CRF receptor 2 in dopamine neurons. PG - 401-7 AB - 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. FAU - Ungless, Mark A AU - Ungless MA AD - Ernest Gallo Clinic and Research Center and Department of Neurology, University of California, San Francisco, San Francisco, California 94110, USA. FAU - Singh, Vineeta AU - Singh V FAU - Crowder, Tara L AU - Crowder TL FAU - Yaka, Rami AU - Yaka R FAU - Ron, Dorit AU - Ron D FAU - Bonci, Antonello AU - Bonci A LA - eng GR - K23 NS42072/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Neuron JT - Neuron JID - 8809320 RN - 0 (CRF receptor type 2) RN - 0 (Carrier Proteins) RN - 0 (Receptors, Corticotropin-Releasing Hormone) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 134773-81-2 (corticotropin releasing factor-binding protein) RN - 9015-71-8 (Corticotropin-Releasing Hormone) RN - VTD58H1Z2X (Dopamine) SB - IM CIN - Neuron. 2003 Jul 31;39(3):387-8. PMID: 12895412 MH - Animals MH - Carrier Proteins/*physiology MH - Corticotropin-Releasing Hormone/pharmacology/*physiology MH - Dopamine/*metabolism MH - In Vitro Techniques MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neurons/drug effects/*metabolism MH - Patch-Clamp Techniques MH - Receptors, Corticotropin-Releasing Hormone/*physiology MH - Receptors, N-Methyl-D-Aspartate/*metabolism EDAT- 2003/08/05 05:00 MHDA- 2003/09/03 05:00 CRDT- 2003/08/05 05:00 PHST- 2003/08/05 05:00 [pubmed] PHST- 2003/09/03 05:00 [medline] PHST- 2003/08/05 05:00 [entrez] AID - S0896627303004616 [pii] AID - 10.1016/s0896-6273(03)00461-6 [doi] PST - ppublish SO - Neuron. 2003 Jul 31;39(3):401-7. doi: 10.1016/s0896-6273(03)00461-6.