Decreased Brain Dopamine Synthesis Rate and Increased [³H]Spiroperidol Binding in Streptozotocin‐Diabetic Rats

Abstract

The rate of accumulation of 3,4-dihydroxy-phenylalanine following decarboxylase inhibition and of homovanillic acid following probenecid treatment were significantly decreased in streptozotocin-diabetic rats. These changes were observed in both the striatum and limbic forebrain. The Bmax for [3H]spiroperidol receptor binding was significantly increased in both brain regions. All of these neurochemical changes were reversed by insulin replacement therapy. Whether these neurochemical changes are attributable to chronic hyperglycemia or some other aspect of the diabetic state is not known.

Bromocriptine Reduces Obesity, Glucose Intolerance and Extracellular Monoamine Metabolite Levels in the Ventromedial Hypothalamus of Syrian Hamsters

“…Moreover, decreases in plasma insulin induced by streptozotocin in rats are associated with decreases in brain tryptophan levels, serotonin synthesis and turnover, and NE turnover which are all restored to normal with insulin replacement therapy [52, 53, 54]. Hyperinsulinemia and insulin resistance are associated with increased sympathetic tone [45].…”

Endocrine Control of Hypothalamic and Pituitary Met-Enkephalin and Beta-Endorphin Contents

“…This suggests that the observed changes are more likely due to the lack of insulin than the severe catabolic state resulting from it. Whether or not dopaminergic and adrenergic mecha nisms are involved remains unknown, although a decrease in dopamine metabolism in the brain of diabetic rats has been re ported [41],…”

Decreased [3H] YM-09151-2 binding to dopamine D2 receptors in the hypothalamus, brainstem and pancreatic islets of streptozotocin-induced diabetic rats

“…An increased D2 receptor density has been observed in some brain regions (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985). Diabetes mellitus is often accompanied by emotional, behavioral, and mood disturbances or some centrally mediated neurological complications (Salkovic and Lackovic, 1987), the pathophysiology of which is still unclear, but might be related to dysfunction of the brain dopaminergic system, as described by several laboratories (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985;Laokovic et al, 1990). …”

“…Dopamine is stored in the secretory granules of the pancreatic islets along with serotonin and calcium and could also be generated in pancreatic islets from its precursor L-dopa (Blanca et al, 2005). Hyperglycemia during diabetes is reported to damage dopaminergic functions, as shown by changes in dopamine metabolism in the human brain and the brains of animals with experimentally induced diabetes (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985;Laokovic et al, 1990). An increased D2 receptor density has been observed in some brain regions (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985).…”

“…Hyperglycemia during diabetes is reported to damage dopaminergic functions, as shown by changes in dopamine metabolism in the human brain and the brains of animals with experimentally induced diabetes (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985;Laokovic et al, 1990). An increased D2 receptor density has been observed in some brain regions (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985). Diabetes mellitus is often accompanied by emotional, behavioral, and mood disturbances or some centrally mediated neurological complications (Salkovic and Lackovic, 1987), the pathophysiology of which is still unclear, but might be related to dysfunction of the brain dopaminergic system, as described by several laboratories (Lozovsky et al, 1981;Trulson and Himmel, 1983;Serri et al, 1985;Laokovic et al, 1990).…”