EFFECTS OF STREPTOZOTOCIN-INDUCED DIABETES ON PRODYNORPHIN-DERIVED PEPTIDES IN RAT-BRAIN REGIONS

Pharmacological studies suggest that diabetes produces changes in the brain opioid system, affecting several behavioral functions including analgesia, feeding and self-stimulation. Previous investigations of opioid receptor binding have failed to explain the unusual opioid pharmacology of the diabetic animal. In the present study, the effects of streptozotocin-induced diabetes on levels of three immunoreactive (ir)-prodynorphin-derived peptides, ir-dynorphin A(1-17) (A(1-17)), ir-dynorphin A(1-8) (A(1-8)) and ir-dynorphin B-1-13 (B-1-13), were determined in eleven brain regions known to be involved in appetite, taste and reward. Diabetes was found to increase levels of A(1-17) in the ventromedial and dorsomedial hypothalamic nuclei (+60% and +25%, respectively) and levels of A(1-8) in the dorsomedial and lateral hypothalamus (+45% and +35%, respectively). The possible significance of these results is discussed in relation to (i) diabetic hyperphagia, (ii) medial hypothalamic transduction of circulating insulin levels, and (iii) the potentiation of reward by metabolic need states.