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Volume 16, Number 24, Issue of December 15, 1996 pp. 8170-8180
Copyright ©1996 Society for Neuroscience

The Hypothalamic Ventromedial Nuclei Couple Activity in the Hypothalamo-Pituitary-Adrenal Axis to the Morning Fed or Fasted State

Received July 9, 1996; revised Sept. 13, 1996; accepted Oct. 1, 1996.

SuJean Choi, Cydney Horsley, Shirley Aguila, and Mary F. Dallman

Department of Physiology, University of California San Francisco, San Francisco, California 94143-0444

Function in the adrenocortical system is markedly altered by availability of food. Basal activity is lowest and stress responsivity highest in the morning when nocturnal rats eat ~90% of their daily calories during the dark. After an overnight fast, basal corticotrophin and corticosteroid levels are elevated, and responsivity to stressors is decreased. Central neural sites that control these changes are unidentified. The hypothalamic ventromedial nuclei (VMN) appear to signal satiety; lesions result in increased food intake, obesity, and elevated basal insulin and corticosteroids. Thus, the VMN are good candidates for calorically mediated control of adrenocortical system function in satiated rats. We injected colchicine into the VMN to cause reversible inhibition of activity () and tested the effects on basal and stimulated function in the adrenocortical system. Colchicine-injected rats that fed ad libitum exhibited increased basal but reduced corticotrophin and corticosterone responses to restraint in the morning compared with controls. By contrast, after an overnight fast, control rats had increased basal adrenocortical hormones and decreased stress responses that did not differ from colchicine-injected rats. Colchicine was visualized within cells in the VMN for up to 5 d using fluorescein/colchicine, and the treatment did not cause increased gliosis; moreover, the functional effects of the injections were reversed within 15 d. We conclude that (1) the VMN serve to couple activity in the adrenocortical system to energy intake and (2) discrete colchicine injections provide a behaviorally and neuroendocrinologically useful period of inhibition without causing permanent functional damage.

Key words: adrenocorticotropin; corticosterone; obesity; insulin; reversible inhibition; colchicine

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