The melanocortinergic pathway is rapidly recruited by emotional stress and contributes to stress-induced anorexia and anxiety-like behavior.
Neurons producing melanocortin receptor agonist, alpha-MSH derived from proopiomelanocortin, and antagonist, agouti-related protein, are known to be sensitive to metabolic stress such as food deprivation and glucoprivation. However, how these neurons respond to emotional/psychological stress remained to be elucidated. We report here that acute emotional stressors, i.e. restraint and forced swim, evoked mRNA expression of c-fos, a neuronal activation marker, in a high percentage of proopiomelanocortin neurons (up to 53% for restraint stress and 62% for forced swim), with marked variations along the rostro-caudal axis of the arcuate nucleus. In contrast, only a small population of agouti-related protein neurons in this brain region was activated. These neuronal activation patterns were correlated with behavioral reactions. Both stressors suppressed feeding and induced anxiety-like behavior in the elevated plus-maze test, as reflected by a reduction in the percentage of entries and time spent in the open arms. Central pretreatment with SHU9119, a melanocortin receptor antagonist, dose dependently attenuated the anorectic and anxiogenic effects elicited by acute restraint or forced swim. These results indicate that the melancortinergic pathway can be rapidly recruited by acute emotional stress, and that activation of melanocortin signaling is involved in mediating stress-induced anorexia and anxiety.
Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Jing
J
Liu
Jacob C
JC
Garza
Ha V
HV
Truong
John
J
Henschel
Wei
W
Zhang
Xin-Yun
XY
Lu
D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D000855:Anorexia / Q000209:etiology*; D001007:Anxiety / Q000209:etiology*; D001522:Behavior, Animal / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D020869:Gene Expression Profiling; D016762:Genes, fos; D020738:Leptin / Q000097:blood; D008297:Male; D053486:Melanocortins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood / Q000150:complications* / Q000503:physiopathology*; D013550:Swimming / Q000502:physiology
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D020738:Leptin; D053486:Melanocortins; D011333:Pro-Opiomelanocortin; D003345:Corticosterone