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The Journal of Neuroscience, September 26, 2007, 27(39):10568-10577; doi:10.1523/JNEUROSCI.3044-06.2007

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Behavioral/Systems/Cognitive
Stimulation of Lateral Septum CRF₂ Receptors Promotes Anorexia and Stress-Like Behaviors: Functional Homology to CRF₁ Receptors in Basolateral Amygdala

Vaishali P. Bakshi,¹ Sarah M. Newman,³ Stephanie Smith-Roe,⁴ Kimberly A. Jochman,² and Ned H. Kalin¹

Departments of ¹Psychiatry and ²Surgery and ³Neuroscience Training Program, University of Wisconsin–Madison, Madison, Wisconsin 53719, and ⁴Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon 97331

Correspondence should be addressed to Dr. Vaishali P. Bakshi, Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719. Email: vbakshi{at}wisc.edu

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 CRF₁/CRF₂ receptor agonist urocortin. Separate groups of food-restricted male Sprague Dawley rats were given infusions of urocortin (0, 50, 125, 250 ng/0.5 µl) 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 dose-dependently 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 CRF₁/CRF₂ receptor antagonist D-Phe-CRF_(12–41) (0, 100, 1000 ng/0.5 µl) or the novel selective CRF₂ receptor antagonist Astressin2B (0, 500, 1000 ng/0.5 µl) blocked urocortin-induced effects, but the CRF₁-selective antagonist NBI27914 (0, 500, 1000 ng/0.5 µl) 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 CRF₂ receptors within the LS.

Key words: corticotropin-releasing factor; corticotropin-releasing hormone; CRH; ingestive behavior; anxiety; amygdala

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Received July 18, 2006; revised Aug. 3, 2007; accepted Aug. 4, 2007.

Correspondence should be addressed to Dr. Vaishali P. Bakshi, Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719. Email: vbakshi{at}wisc.edu

This article has been cited by other articles:

				J. Gay, E. Kokkotou, M. O'Brien, C. Pothoulakis, and K. P. Karalis Corticotropin-Releasing Hormone Deficiency Is Associated with Reduced Local Inflammation in a Mouse Model of Experimental Colitis Endocrinology, July 1, 2008; 149(7): 3403 - 3409. [Abstract] [Full Text] [PDF]

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