Decreased levels of neuropeptide Y5 receptor binding sites in two experimental models of epilepsy

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, [I-125][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%) 1 h after a kindled seizure. Additionally, Y-5 receptor binding sites in the hippocampus and in the neocortex were unchanged 6 h after kainic acid injection, but were highly reduced at 12 and 24 h. 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. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.