Corticotropin-releasing hormone receptor subtypes and emotion

Preclinical data indicate that corticotropin-releasing hormone (CRH) has anxiogenic properties and a dysregulation in CRH systems has been suggested to play a role in a variety of stress-related psychiatric disorders, such as anxiety, depression, and eating disorders. Two CRH receptor subtypes have been identified, termed CRH1 receptor (CRH1) and CRH2 receptor (CRH2), with its splice variants CRH2 alpha and CRH2 beta. These receptor subtypes differ in their pharmacology and expression pattern in the brain. Mouse mutants in which the CRH1 receptor subtype has been deleted show an impaired stress response, reduced anxiety-related behavior, and cognitive deficits. Studies using antisense oligodeoxynucleotides directed against CRH1 or CRH2 alpha identified the CRH1 receptor as the main target for CRH in mediating anxiogenesis, although recent data also suggest a possible role for CRH2 alpha. More clearly, CRH2 alpha is involved in the CRH effects on food intake. Moreover, local injection of CRH into areas rich in CRH2 alpha also result in altered sexual female behavior. Therefore, it is suggested that the CRH2 alpha may primarily influence a system concerned with implicit processes necessary for survival, i.e., with motivational types of behavior including feeding, reproduction, and possibly defense, whereas the CRH1 may be more concerned with explicit processes, including attention, executive functions, the conscious experience of emotions, and possibly learning and memory related to these emotions. This also suggests that patients suffering from anxiety and depression may benefit from treatment with CRH1 antagonistic drugs, while drugs targeting CRH2 alpha may be of particular benefit for patients with eating disorders.