One of the important underlying mechanisms for developing alcohol abuse and relapse is negative reinforcement whereby alcohol reduces anxiety and other negative feelings, some of which occur in reaction to stress (Sinha, 2001). CRH (CRF) is well known to mediate unconditioned and conditioned anxiety response after exposure to stress, and maladaptive responses to stress increase alcohol consumption and relapse (Koob, 1999; Sinha, 2001; Zimmermann et al., 2004). Given the relationship among stress, alcohol abuse, and the CRH system, we hypothesized that CRHR1 is involved in the development of alcohol dependence as well as the abnormality of brain oscillations that have been shown to be associated with such dependence. In particular, a recent study demonstrated that both CRH and ethanol enhanced GABA-mediated neurotransmission in central amygdala neurons from wild-type and Crhr2 knockout mice, but not Crhr1 knockout mice (Nie et al., 2004). CRHR1 receptor (but not CRHR2) antagonists blocked both CRH and ethanol effects in wild-type mice (Nie et al., 2004). These results suggest a pivotal role of CRHR1 receptor in modulating ethanol enhancement of GABAergic synaptic transmission in the central
