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

Streptozotocin (STZ)-induced diabetes and chronic food restriction have both been reported to lower thresholds for lateral hypothalamic self-stimulation (LHSS). In view of recent evidence that insulin regulates monoamine transporter gene expression in brain, it is possible that the hypoinsulinemia that is common to diabetes and food restriction mediates the enhancement of brain stimulation reward. Two experiments were conducted to test predictions of this hypothesis. In Experiment 1, the effect of STZ-induced diabetes on 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 rate than the normophagic HF rats, the two dietary groups displayed similar declines in LHSS threshold, consonant with their nearly identical plasma insulin levels of 25.1+/-2.1 and 24.8+/-0.9 mu IU/ml, respectively. In agreement with observations in food-restricted rats, the lowering of threshold in diabetic rats was preferentially associated with electrode placements adjacent or dorsal to the dorsolateral aspect of the fornix, In Experiment 2, the 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 threshold in ad libitum fed rats and, more transiently, reversed the threshold-lowering effect of food restriction. Acute insulin treatment (3 mU, 15 min prior) also elevated threshold in food-restricted rats. These results rue consistent with the hypothesis that insulin modulates sensitivity of a brain reward system and that hypoinsulinemia may be the common factor in food restriction and diabetes that accounts for the enhancement of perifornical LHSS. (C) 2000 Elsevier Science B.V. All rights reserved.