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 CNS to adenosine and gamma-aminobutyric acid (GABA) in diabetes. The effects of adenosine, 2-chloroadenosine, GABA, muscimol and baclofen were studied on orthodromic synaptic potentials recorded in the CA1 region of slices taken from normal rats or animals made diabetic by the injection of streptozotocin. 2. In diabetic animals the sensitivity to adenosine 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 adenosine 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 baclofen. 5. Treatment of diabetic animals with insulin restored the potency of adenosine to control levels. 6. It is concluded that the diabetic state is accompanied by substantial changes of adenosine sensitivity due to the loss of nucleoside uptake processes. Secondary neurochemical changes following from this in human diabetic patients may contribute to the reported behavioural changes.