The Role of Corticotropin-Releasing Hormone in the Dorsal Raphe Nucleus in Mediating the Behavioral Consequences of Uncontrollable Stress

• Published in: The Journal of neuroscience 2002-02, Vol.22 (3), p.1020-1026
• Main Authors: Hammack, Sayamwong E, Richey, Kristen J, Schmid, Megan J, LoPresti, Matthew L, Watkins, Linda R, Maier, Steven F
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Conditioning, Psychological - drug effects; Conditioning, Psychological - physiology; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - analogs & derivatives; Corticotropin-Releasing Hormone - antagonists & inhibitors; Corticotropin-Releasing Hormone - metabolism; Dose-Response Relationship, Drug; Electroshock; Escape Reaction - drug effects; Escape Reaction - physiology; Helplessness, Learned; Injections, Intraventricular; Male; Microinjections; Organ Specificity - drug effects; Raphe Nuclei - drug effects; Raphe Nuclei - metabolism; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; Stress, Physiological - physiopathology
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/jneurosci.22-03-01020.2002

Inescapable shock (IS) produces subsequent interference with escape behavior and increased fear conditioning that has been linked to increased activity and release of serotonin (5-HT) from neurons within the caudal dorsal raphe nucleus (DRN) both at the time of IS and later behavioral testing. Extrahypothalamic corticotropin-releasing hormone (CRH) has been implicated in many stress-related phenomena and has recently been shown to increase DRN 5-HT activity in the same caudal DRN area at which IS increases 5-HT activity. The current set of studies therefore examined the role of CRH in mediating the behavioral sequelae of IS. Intra-DRN microinjection of the nonselective CRH receptor antagonist d-Phe CRH (12-41) blocked the IS-induced behavioral changes when administered before IS but not when administered before later behavioral testing. Furthermore, intra-DRN administration of CRH in the absence of IS dose-dependently mimicked the effects of IS and interfered with escape behavior and increased fear conditioning 24 hr later. This effect was specific to injection of CRH into the caudal DRN and was not produced by microinjection into the rostral DRN. Intracerebroventricular CRH produced escape deficits and potentiated fear conditioning 24 hr later at only much higher doses, further confirming the site specificity of the effects. The potential role of the caudal DRN in states of anxiety is discussed.