MICRODIALYSIS STUDY OF MODIFICATION OF HYPOTHALAMIC NEUROTRANSMITTERSIN STREPTOZOTOCIN-DIABETIC RATS

Neurochemical changes in the ventromedial hypothalamus (VMH) after a s ingle intravenous injection of streptozotocin were examined, using in vivo brain microdialysis under free-moving conditions. Although strept ozotocin-induced diabetes produced significant decreases in extracellu lar concentrations of noradrenaline (NA), serotonin (5-HT), and their metabolites in the VMH, the ratios of 3-methoxy-4-hydroxyphenylglycol/ NA and 5-hydroxyindoleacetic acid (5-HIAA)/5-HT were increased. Experi mental diabetes led to a pronounced increase in extracellular GABA, wh ich correlated strongly with the decrease in dialysate levels of NA, a nd to a smaller extent with that of 5-HT. A modification of dopamine ( DA) metabolism was induced in the VMH of diabetic rats, whereas there was no change in dialysate DA levels. Daily injections of insulin were able to restore their levels to normal in the areas tested in the mic rodialysis study. The equal increases in dialysate 5-HT and 5-HIAA and the better restoration of the 5-HIAA/5-HT ratio after insulin therapy indicate that serotonergic activity may depend on the levels of circu lating insulin more than on noradrenergic activity. Circulating NA was reduced in streptozotocin-diabetic rats, suggesting that the diabetes -induced reduction in sympathetic activity is accompanied by decreases in NA, or 5-HT, or both, in the VMH.