Decreased levels of neuropeptide Y(5) receptor binding sites in two experimental models of epilepsy

Abstract

It has been suggested that the anticonvulsant effects of neuropeptide Y (NPY) could be mediated by the activation of Y(2) and/or Y(5) receptors. NPY Y(1) receptor levels are known to decrease and Y(2) to increase in rat models of epilepsy. By using an autoradiographic approach, we investigated whether epilepsy models (kainic acid and kindling) are also associated with changes in Y(5) receptors. Compared with naive controls, [125I][Leu(31), Pro(34)]PYY/BIBP3226-insensitive (Y(5)) binding sites in the hippocampus (strata oriens and radiatum of CA3 and CA1) and in the neocortex (superficial layers) were unchanged in sham-stimulated rats, but reduced by approximately 50% in kindled rats (seven days after the last stimulus evokes seizure), and further reduced (to approximately -90%) 1h after a kindled seizure. Additionally, Y(5) receptor binding sites in the hippocampus and in the neocortex were unchanged 6h after kainic acid injection, but were highly reduced at 12 and 24h. No changes in Y(5) binding levels were found in the dentate gyrus and the pyramidal cell layer of the hippocampus. The present data suggest that changes in Y(5) receptor levels occur in epilepsy models. These changes may play a role in seizure expression and/or in the maintenance of kindling hyperexcitability.