CHANGES IN ADENOSINE SENSITIVITY IN THE HIPPOCAMPUS OF RATS WITH STREPTOZOTOCIN-INDUCED DIABETES

1 Hippocampal slices have been used to assess the sensitivity of the C NS to adenosine and gamma-aminobutyric acid (GABA) in diabetes. The ef fects of adenosine, 2-chloroadenosine, GABA, muscimol and baclofen wer e studied on orthodromic synaptic potentials recorded in the CA1 regio n of slices taken from normal rats or animals made diabetic by the inj ection of streptozotocin. 2 In diabetic animals the sensitivity to ade nosine was increased 4 fold compared with normal rats. The potency of 2-chloroadenosine was unchanged. 3 The nucleoside transport inhibitor, hydroxynitrobenzylthioinosine (HNBTI), increased the potency of adeno sine in slices from normal rats but not in slices from diabetic rats. 4 No change was observed in the potency of GABA or muscimol, although a small but significant decrease was detected in the EC50 value for ba clofen. 5 Treatment of diabetic animals with insulin restored the pote ncy of adenosine to control levels. 6 It is concluded that the diabeti c state is accompanied by substantial changes of adenosine sensitivity due to the loss of nucleoside uptake processes. Secondary neurochemic al changes following from this in human diabetic patients may contribu te to the reported behavioural changes.