Stimulation of Lateral Septum CRF₂Receptors Promotes Anorexia and Stress-Like Behaviors: Functional Homology to CRF₁Receptors in Basolateral Amygdala

Abstract

The corticotropin-releasing factor (CRF) system is the primary central mediator of stress-like states, coordinating behavioral, endocrine, and autonomic responses to stress. Although induction of anorexia is a well documented effect of CRF receptor agonist administration, the central sites and behavioral processes underlying this phenomenon are poorly understood. The present studies addressed this question by examining the neuroanatomical, behavioral, and pharmacological mechanisms mediating decreases in feeding produced by the CRF 1 /CRF 2 receptor agonist urocortin. Separate groups of food-restricted male Sprague Dawley rats were given infusions of urocortin (0, 50, 125, 250 ng/0.5 l) into the lateral septum (LS) and immediately afterward were rated on a wide array of behaviors (locomotion, rearing, grooming, stereotypies) including a microstructural analysis of ingestive behavior. Intra-LS urocortin infusion dosedependently reduced feeding and drinking while concomitantly increasing grooming, stereotypies, and ethological plus traditional measures of anxiety-like responses in the elevated plus-maze. Urocortin infusion into neighboring sites (lateral ventricle, medial caudate) had no effects. Coinfusion into the LS of the mixed CRF 1 /CRF 2 receptor antagonist D-Phe-CRF (12-41) (0, 100, 1000 ng/0.5 l) or the novel selective CRF 2 receptor antagonist Astressin2B (0, 500, 1000 ng/0.5 l) blocked urocortin-induced effects, but the CRF 1 -selective antagonist NBI27914 (0, 500, 1000 ng/0.5 l) had no effect, although it completely reversed the behavioral sequelae of CRF when infused into the basolateral amygdala. These results indicate that one of the modes through which the CRF system promotes anorexia is the recruitment of stress-like states after stimulation of CRF 2 receptors within the LS.

Restraint stress increases serotonin release in the central nucleus of the amygdala via activation of corticotropin-releasing factor receptors

“…The finding that central CRF receptor mechanisms mediate stress-induced CeA 5-HT release supports a growing body of literature demonstrating central CRF receptor-mediated regulation of stress responses, anxiety, anorexia and 5-HT release in a variety of the limbic brain regions [for example, 4,16,23,26,28,39,40,42]. However, this is the first report of CRF-mediation of stressinduced 5-HT release in the amygdala.…”

“…The voltage output was recorded by CSW32 v1. 4 Chromatography Station for Windows (DataApex, Prague, Czech Republic). Elution time for 5-HT was 11-13 min, and individual 5-HT peaks were identified by comparison to a 5-HT standard (7.9 pg/5 μl).…”

Distribution and targets of the relaxin‐3 innervation of the septal area in the rat

“…Infusion of urocortin, a CRF family peptide, into the lateral septum induced anorectic effects that may be secondary to stress driven anxiety-like behavior (Bakshi et al, 2007). Notably, the location of the injections in these experiments coincides with the distribution of RLN3-positive fibers in the LSr-vl.…”

Urocortin 1 reduces food intake and ghrelin secretion via CRF2 receptors

“…In addition, the initial effect of food intake inhibition after central UCN injection is absent in mice lacking CRF 1 receptors (4). Whereas CRF 1 receptors mediate immediate mobilization of avoidance, defensive responses to threats, and acute interruption of feeding and digestion, CRF 2 receptors mediate long-term responses by postponing appetite and digestion and modulating anxiety-like behaviors (57). Furthermore, CRF 1 and CRF 2 receptor pathways play important roles in stress-related alterations of feeding behavior and gut motor functions (41).…”