The results of these investigations provide new insights into the correlation between alcohol abuse, the negative effects of stress and anxiety, and the function of different neuropetidergic systems. Of particular interest are data showing that progression of ethanol dependence can be facilitated by innate high sensitivity to stress or by recruitment of stress mechanisms by a history of ethanol intoxication. It has been shown, for example, that high ethanol drinking msP rats carry a mutation of the gene encoding for the CRH1R protein, conferring on these animals high sensitivity to stress and anxiety-like behavior that are attenuated by ethanol drinking. Interestingly, in these rats treatment with selective CRH1R antagonists like MTIP attenuates ethanol self-administration and relapse to ethanol seeking. Similar, but less robust effects of MTIP were observed in postdependent Wistar rats, while nondependent animals are less sensitive to inhibition of CRH neurotransmission.
