Diabetes mellitus: stress, neurochemistry and behavior

Neurochemical alterations in several rodent models of insulin-dependent diabetes are compared and their relevance to behavioral and physiological pathology in the clinical disorder is discussed. In the majority of rodent models, reductions in metabolism of norepinephrine (NE), dopamine (DA) and serotonin (5HT) in the central nervous system (CNS) have been reported. While there are two reports of increased 5HT turnover in CSF or post-mortem brains of diabetic humans experiencing severe ketoacidosis, these patients were receiving insulin therapy. Insulin appears to have effects on monoamines opposite to that of chronic hyperglycemia. Both in rodent models and in clinical populations, there is widespread evidence of enhanced hormonal and behavioral responsiveness to stress. There are findings in rodent models indicating that hormonal responses to stress are related to CNS monoamine activity. The mechanisms responsible for both hormonal and CNS alterations in diabetes, as well as their involvement in behavioral pathology, can best be investigated further using animal models.