Overexpression of agouti protein and stress responsiveness in mice

• Published in: Physiology & behavior 2001-07, Vol.73 (4), p.599-608
• Main Authors: Harris, Ruth B.S., Zhou, Jun, Shi, Mingxia, Redmann, Stephen, Mynatt, Randall L., Ryan, Donna H.
• Format: Article
• Language: English
• Subjects: ACTH; Adrenocorticotropic Hormone - blood; Affectivity. Emotion; Agouti protein; Agouti Signaling Protein; Animals; Anxiety; Biogenic Monoamines - metabolism; Biological and medical sciences; Body weight; Body Weight - physiology; Brain Chemistry - physiology; Corticosterone - blood; Corticosterone - metabolism; Corticotropin-Releasing Hormone - metabolism; Eating - physiology; Fundamental and applied biological sciences. Psychology; Genotype; Hypothalamus - metabolism; Intercellular Signaling Peptides and Proteins; Male; Melanocortin receptors; Organ Size - physiology; Personality. Affectivity; Protein Biosynthesis; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Restraint stress; Restraint, Physical; Stress, Psychological - metabolism; Stress, Psychological - psychology; αMSH
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/S0031-9384(01)00508-X

Ectopic overexpression of agouti protein, an endogenous antagonist of melanocortin receptors' linked to the β-actin promoter (BAPa) in mice, produces a phenotype of yellow coat color, Type II diabetes, obesity and increased somatic growth. Spontaneous overexpression of agouti increases stress-induced weight loss. In these experiments, other aspects of stress responsiveness were tested in 12-week-old male wild-type mice and BAPa mice. Two hours of restraint on three consecutive days produced greater increases in corticosterone and post-stress weight loss in BAPa than wild-type mice. In Experiment 2, anxiety-type behavior was measured immediately after 12 min of restraint. This mild stress did not produce many changes indicative of anxiety, but BAPa mice spent more time in the dark side of a light–dark box and less time in the open arms of an elevated plus maze than restrained wild-type mice. In a defensive withdrawal test, grooming was increased by restraint in all mice, but the duration of each event was substantially shorter in BAPa mice, possibly due to direct antagonism of the MC4-R by agouti protein. Thus, BAPa mice showed exaggerated endocrine and energetic responses to restraint stress with small differences in anxiety-type behavior compared with wild-type mice. These results are consistent with observations in other transgenic mice in which the melanocortin system is disrupted, but contrast with reports that acute blockade of central melanocortin receptors inhibits stress-induced hypophagia. Thus, the increased stress responsiveness in BAPa mice may be a developmental compensation for chronic inhibition of melanocortin receptors.