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Abstract for presentation at ISBRA 2006 World Congress on Alcohol Research
Symposium No: 44

Corticotrophin releasing factor-binding protein (CRF-BP) as a novel target for the treatment of alcohol dependence

  • Dr. Selena Bartlett, Ernest Gallo Clinic and Research Center, University of California San Francisco, United States
  • Mr. Jeff Simms, Ernest Gallo Clinic and Research Center, University of California San Francisco, United States
  • Dr. Carsten Nielsen, Ernest Gallo Clinic and Research Center, University of California San Francisco, United States
  • Dr. Antonello Bonci, Ernest Gallo Clinic and Research Center, University of California San Francisco, United States

One of the most difficult aspects in treating alcohol dependence is the relapse to uncontrolled drinking that frequently occurs after a period of abstinence. Factors such as stress and exposure to situations previously associated with alcohol drinking (referred to as "cues") are found to contribute to relapse drinking. Corticotrophin releasing factor (CRF) is a 41-aa peptide that has been shown to induce various behavioral changes related to adaptation to stress. The multiple actions of CRF are mediated by two classes of specific CRF receptors, CRF-R1 and CRF-R2. The CRF-BP binds CRF with high affinity and it was principally believed to inhibit its physiological actions in the periphery. CRF-BP is also present in the central nervous system and in contrast to the periphery, where CRF-BP is circulating, it is membrane-bound and this may be important for its activity. In fact, CRF interaction with CRF-BP may positively modulate the CRF-R2 function. It was shown that the interaction of CRF-R2s and CRF-BP by CRF is necessary to potentiate NMDA receptor currents in the ventral tegmental area (VTA) (Ungless et al., 2003). CRF has also been shown to play a key role in stress-induced reinstatement of cocaine seeking (Wang et al., 2005). We hypothesized that by inhibiting CRF binding to CRF-BP, it may be possible to modulate ethanol-mediated behaviors. We have shown that inhibiting CRF-BP reduces ethanol consumption in the voluntary 2 bottle choice paradigm. We will also show results from cell based assays developed to screen compounds that inhibit CRF-BP. Support Contributed By: State of California for medical research on alcohol and substance abuse through the University of California, San Francisco (UCSF) to S.E.B. and A.B and Department of Defense to S.E.B and A.B.

Ungless et al., Neuron. 2003 Jul 31;39(3):401-7.
Wang et al., J. Neuroscience. 2005 Jun1;25(22):5389-96.