Hypoinsulinemia may mediate the lowering of self-stimulation thresholds byfood restriction and streptozotocin-induced diabetes

Streptozotocin (STZ)-induced diabetes and chronic food restriction have bot h been reported to lower thresholds for lateral hypothalamic self-stimulati on (LHSS). In view of recent evidence that insulin regulates monoamine tran sporter gene expression in brain, it is possible that the hypoinsulinemia t hat is common to diabetes and food restriction mediates the enhancement of brain stimulation reward. Two experiments were conducted to test prediction s of this hypothesis. In Experiment 1, the effect of STZ-induced diabetes o n threshold for LHSS was monitored in rats maintained on either a high fat (HF; 64% fat/0% carbohydrate) or high carbohydrate (HC; 60% carbohydrate/4% fat) diet. Although HC rats were hyperphagic and lost weight at a faster r ate than the normophagic HF rats, the two dietary groups displayed similar declines in LHSS threshold, consonant with their nearly identical plasma in sulin levels of 25.1+/-2.1 and 24.8+/-0.9 mu IU/ml, respectively. In agreem ent with observations in food-restricted rats, the lowering of threshold in diabetic rats was preferentially associated with electrode placements adja cent or dorsal to the dorsolateral aspect of the fornix, In Experiment 2, t he effect of subchronic intracerebroventricular (i.c.v.) insulin treatment on LHSS threshold was determined in ad libitum fed and food-restricted rats . A five day regimen of i.c.v. insulin (3 mU twice per day) produced a long -lasting (>7 days beyond cessation of insulin treatment) elevation of thres hold in ad libitum fed rats and, more transiently, reversed the threshold-l owering effect of food restriction. Acute insulin treatment (3 mU, 15 min p rior) also elevated threshold in food-restricted rats. These results rue co nsistent with the hypothesis that insulin modulates sensitivity of a brain reward system and that hypoinsulinemia may be the common factor in food res triction and diabetes that accounts for the enhancement of perifornical LHS S. (C) 2000 Elsevier Science B.V. All rights reserved.