title: Corticotropin-releasing factor in the norepinephrine nucleus, locus coeruleus, facilitates behavioral flexibility.
abstract: Corticotropin-releasing factor (CRF), the stress-related neuropeptide, acts as a neurotransmitter in the brain norepinephrine nucleus, locus coeruleus (LC), to activate this system during stress. CRF shifts the mode of LC discharge from a phasic to a high tonic state that is thought to promote behavioral flexibility. To investigate this, the effects of CRF administered either intracerebroventricularly (30-300 ng, i.c.v.) or directly into the LC (intra-LC; 2-20 ng) were examined in a rat model of attentional set shifting. CRF differentially affected components of the task depending on dose and route of administration. Intracerebroventricular CRF impaired intradimensional set shifting, reversal learning, and extradimensional set shifting (EDS) at different doses. In contrast, intra-LC CRF did not impair any aspect of the task. The highest dose of CRF (20 ng) facilitated reversal learning and the lowest dose (2 ng) improved EDS. The dose-response relationship for CRF on EDS performance resembled an inverted U-shaped curve with the highest dose having no effect. Intra-LC CRF also elicited c-fos expression in prefrontal cortical neurons with an inverted U-shaped dose-response relationship. The number of c-fos profiles was positively correlated with EDS performance. Given that CRF excites LC neurons, the ability of intra-LC CRF to activate prefrontal cortical neurons and facilitate EDS is consistent with findings implicating LC-norepinephrine projections to medial prefrontal cortex in this process. Importantly, the results suggest that CRF release in the LC during stress facilitates shifting of attention between diverse stimuli in a dynamic environment so that the organism can adapt an optimal strategy for coping with the challenge.
authors: The University of Pennsylvania, Philadelphia, PA, USA.
authors: Kevin
authors: K
authors: Snyder
authors: Wei-Wen
authors: WW
authors: Wang
authors: Rebecca
authors: R
authors: Han
authors: Kile
authors: K
authors: McFadden
authors: Rita J
authors: RJ
authors: Valentino
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology
chemical_list: D003346:Corticotropin-Releasing Hormone