Our studies in the role of stress in drug abuse have continued. We and others have shown that stress can play an important role in promoting drug self-administration and relapse to drug abuse. The corticotropin releasing hormone receptor (CRHR1) plays a central role in initiation of the response to stress. Our studies suggest that CRHR1 antagonists such as antalarmin may be useful in the treatment of human alcohol dependence and relapse to other drugs of abuse, and that optimal treatment may vary between different subtypes of patients. We studied compulsive eating in the rat and found that rats withdrawn from intermittent access to palatable food (analogous to human dieting) exhibit overeating of palatable food upon renewed access and an affective withdrawal-like state characterized by CRH1 receptor antagonist-reversible behaviors, including hypophagia, motivational deficits to obtain less palatable food, and anxiogenic-like behavior. Withdrawal was accompanied by increased CRH expression and CRH1 electrophysiological responsiveness in the central nucleus of the amygdala. We propose that recruitment of anti-reward extrahypothalamic CRH1 systems during withdrawal from palatable food, analogous to abstinence from abused drugs, may promote compulsive selection of palatable food, undereating of healthier alternatives, and a negative emotional state when intake of palatable food is prevented.
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