Duration of streptozotocin diabetes influences the response of hypothalamic serotonin metabolism to immobilization stress.
Neurochemical and metabolic effects of acute (immobilization for 2 h) and chronic (immobilization for 2 h/day for 4 consecutive days) stress were investigated in diabetic female rats either pretreated 1 week or 5 weeks earlier with streptozotocin (STZ). Hypothalamic serotonin (5-hydroxytryptamine, 5-HT) metabolism was estimated by measuring the respective levels of 5-HT precursor, the amino acid tryptophan (TRP), 5-HT and the 5-HT metabolite, namely 5-hydroxyindoleacetic acid (5-HIAA). To assess the respective metabolic effects of stress and diabetes, plasma total TRP, insulin, glucose and corticosterone levels were measured. Short- and long-term STZ treatment triggered marked decreases in plasma total TRP and hypothalamus TRP levels but the diabetogenic agent diminished 5-HT metabolism in the 1-week ST-treated rats only. Acute stress promoted a marked decrease in plasma total TRP in the vehicle-treated rats and in the 1-week-diabetic rats, which was associated with significant increases in hypothalamic TRP and 5-HIAA levels. In the 5-week-diabetic rats, a single restraint affected neither peripheral and central TRP levels nor hypothalamus 5-HT metabolism. Acute stress triggered hypercorticosteronemia in all groups of rats but it promoted hyperglycemia and hypoinsulinemia in the vehicle-injected rats only. Twenty-four hours after the fourth immobilization, plasma total TRP was reduced in the vehicle-injected rats only with no effect on hypothalamic levels of TRP. On the other hand, chronic restraint was found to reduce exclusively hypothalamus 5-HT and 5-HIAA levels in the 5-week-diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Chaouloff
F
F
Laboratoire de Pharmacologie, INSERM U7, CHU Necker, Paris, France.
Laude
D
D
Mérino
D
D
Serrurier
B
B
Baudrie
V
V
Elghozi
J L
JL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012149:Restraint, Physical; D012701:Serotonin / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D013997:Time Factors; D014364:Tryptophan / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D003345:Corticosterone