Details

Autor(en) / Beteiligte

• Lemos, Julia C.
• Wanat, Matthew J.
• Smith, Jeffrey S.
• Reyes, Beverly A. S.
• Hollon, Nick G.
• Van Bockstaele, Elisabeth J.
• Chavkin, Charles
• Phillips, Paul E. M.

Titel

Severe stress switches CRF action in the nucleus accumbens from appetitive to aversive

Ist Teil von

• Nature (London), 2012-10, Vol.490 (7420), p.402-406

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2012

Quelle

Psychology & Behavioral Sciences Collection

Beschreibungen/Notizen

• The neuropeptide corticotropin-releasing factor (CRF) acts in the nucleus accumbens of mice to increase dopamine release through coactivation of CRF receptor 1 (CRFR1) and CRFR2, but exposure to severe stress results in loss of this regulation and a switch in the reaction to CRF from appetitive to aversive. How stress deepens depression Severe stress can exacerbate major depression, characterized by a shift from engagement with the environment to withdrawal. Paul Phillips and colleagues now identify a cellular mechanism involved in this shift. Using a mouse model, they find that corticotrophin-releasing factor (CRF), a stress-response-related neuropeptide, increases dopamine release in the nucleus accumbens, but that this regulation is lost after exposure to acute stress. Animals also show opposing responses to CRF application before and after stress. The authors suggest that severe stress switches the emotional response to stressful stimuli, and that this may be central to stress-induced depressive disorders. Stressors motivate an array of adaptive responses ranging from ‘fight or flight’ to an internal urgency signal facilitating long-term goals 1 . However, traumatic or chronic uncontrollable stress promotes the onset of major depressive disorder, in which acute stressors lose their motivational properties and are perceived as insurmountable impediments 2 . Consequently, stress-induced depression is a debilitating human condition characterized by an affective shift from engagement of the environment to withdrawal 3 . An emerging neurobiological substrate of depression and associated pathology is the nucleus accumbens, a region with the capacity to mediate a diverse range of stress responses by interfacing limbic, cognitive and motor circuitry 4 . Here we report that corticotropin-releasing factor (CRF), a neuropeptide released in response to acute stressors 5 and other arousing environmental stimuli 6 , acts in the nucleus accumbens of naive mice to increase dopamine release through coactivation of the receptors CRFR1 and CRFR2. Remarkably, severe-stress exposure completely abolished this effect without recovery for at least 90 days. This loss of CRF’s capacity to regulate dopamine release in the nucleus accumbens is accompanied by a switch in the reaction to CRF from appetitive to aversive, indicating a diametric change in the emotional response to acute stressors. Thus, the current findings offer a biological substrate for the switch in affect which is central to stress-induced depressive disorders.