Effect of nicotinamide on the uptake and release of serotonin and GABA by cerebral cortex synaptosomes in rats with diabetes

Studies of neurotransmitter uptake and release by isolated rats brain cortex synaptosomes demonstrated that [2-14C]serotonin uptake was by 41% lower in streptozotocin-diabetic rats as compared to control. The [U-14C]GABA uptake was considerably elevated. [2-14C]serotonin and [U-14C]GABA release from the neurotransmitter pre-loaded synaptosomes showed significant elevation, especially during the first 3 minutes.

Nicotinamide (NAm) administration (200 mg/kg body weight daily, 14 days) to diabetic rats restored synaptosomal serotonin uptake up to control levels, while the GABA uptake tended to decrease in diabetic rats. With this dose of NAm the partial restoration of serotonin and GABA release was achieved.

The modulating effect of in vivo administered NAm acts via NAD which binds specifically with synaptic membranes. It has been shown that brain NAD(P)/NAD(P)H decreased while sorbitol level increased in streptozotocin-diabetic rats as compared to control. The NAm administration to diabetic rats is accompanied by the increase of NAD(P)/NAD(P)H and the reduction of brain sorbitol level. Data obtained confirm the important role of NAm in the pathogenesis of diabetic encephalopathies.

About the Authors

Donchenko GV, Kuchmerovskaia TM, Parkhomets PK, Obrosova IG, Klimenko AP, Efimov AS. (1995) Effect of nicotinamide on the uptake and release of serotonin and GABA by cerebral cortex synaptosomes in rats with diabetes induced by streptozotocin. Ukr Biokhim Zh. 1995 Jan-Feb;67(1):105-11.