Interaction of the corticotropin hormone receptor subtype 1 with the dopaminergic system in alcohol dependence

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Laura Broccoli, Wolfgang H. Sommer, Rainer Spanagel, Anita C. Hansson
Institute of Psychopharmacology, Central Institute of Mental Health Mannheim, Medical Faculty of Mannheim, Heidelberg University, Mannheim, DE

A large body of preclinical and clinical evidence points to up-regulated corticotropin releasing hormone (CRH) and CRH receptor subtype 1 (CRHR1) signaling within the amygdala as a mechanism underlying the pathology of anxiety disorders, depression and alcoholism. Dopamine (DA) is a key neurotransmitter system involved in the acquisition of alcohol reinforcement and maintenance of voluntary alcohol consumption. Our data establish a functional interaction between co-localized CRHR1 and dopamine D1 receptor in regulating affective behavior, thus representing a novel mechanism of amygdala function. The relevance of this interaction become significant in alcohol dependence where CRHR1-D1 receptor interactions seem to be critical involved in mechanisms leading to increased stress vulnerability and thus triggering stress-induced relapse to alcohol drinking. We further obtained first evidence that another population of CRHR1 residing in DAergic neurons is regulating stress-induced escalation of alcohol consumption in healthy animals. These findings lead to our working hypothesis that DAergic CRHR1 related mechanisms are involved in the transition from social drinking to dependence, while in dopaminoceptive neurons CRHR1-D1 receptor interactions are involved in behavioral stress responses and thus are an important factor in maintaining the dependent state.