Altered behavior and neurochemistry during short-term insulin withdrawal in streptozocin-induced diabetic rats

Amphetamine-induced stereotypy and turnover of dopamine (DA) and serotonin (5-HT) in the CNS were assessed in streptozocin-induced diabetic rats 48 h after withdrawal from insulin treatment and compared with nondiabetic controls, diabetic rats receiving continued insulin treatment, and chronically hyperglycemic diabetic rats. Stereotypy was attenuated in chronically hyperglycemic diabetic rats but normalized in insulin-treated diabetic rats. Stereotypy in insulin-withdrawn rats was intermediate, being attenuated significantly relative to controls but not significantly different from either insulin-treated diabetic rats or chronically hyperglycemic diabetic rats. DA turnover was significantly reduced in striatum and hypothalamus in all diabetic groups. 5-HT turnover was reduced in chronically hyperglycemic diabetic rats in all four brain regions but normalized in insulin-treated diabetic rats. Insulin-withdrawn diabetic rats had significantly reduced 5-HT turnover in frontal cortex. Taken together, the findings indicate that insulin replacement does not normalize diabetes-induced reduction in DA turnover and that short-term insulin withdrawal, e.g., occurring clinically with noncompliance, affects both 5-HT turnover in some brain regions and behavior.