Abstracts

Evidence from genetic and pharmacological studies in rodents, and some data in humans, support an anti-seizure action of neuropeptide Y (NPY) in focal, acquired epilepsy. However, the effects of NPY on the seizures in generalized genetic epilepsy remains unexplored. We investigated the effect of exogenously administered NPY on seizures were in a model of genetic generalised epilepsy, Genetic Absence Epilepsy Rats of Strasbourg (GAERS). Adult male GAERS were implanted with extradural electrodes and an intracerebroventricular (icv) cannula. After an initial dose-effect experiment (n=3), saline, 6 and 12 nmol NPY were administered in a random order (n=6). The effect of NPY on seizure activity was quantitated by a 90-minute EEG post-injection recording. The endogeneous regional brain content of NPY was compared between GAERS (n=8) and non-epileptic control (NEC) rats (n=8) using radioimmunoassay on tissue microdissected from the parietal cortex, thalamic ventrobasal complex and reticular thalamic nucleus. The icv injection studies demonstrated a rapid onset and sustained seizure suppression following NPY treatment compared to vehicle, with both 6 and 12 nmol NPY having a decreased median percentage time in seizure (4.7% and 5.3% vs. 12.4%, p=0.028 and 0.043) and number of seizures per minute (0.5 and 0.3 vs. 1.1, p=0.028 and 0.043), and 6 nmol NPY having a decreased average seizure length (6.1 vs. 7.5 sec, p=0.046). There was no significant difference between the degree of seizure suppression between 6 and 12 nmol of NPY (all p[gt]0.05). Tissue NPY content did not differ between GAERS and NEC rats for any region examined. These data study demonstrate that exogenous administration of NPY suppresses of absence seizures in the GAERS. This suggests that NPY modulates pathological oscillatory thalamocortical activity and may represent a new therapeutic approach for the treatment of generalized epilepsies. The lack of difference in the tissue content of NPY in thalamocortical brain regions between GAERS and NEC rats indicates that alterations in NPY expression is unlikely to be a major contributor to the GAERS phenotype. (Supported by The Royal Melbourne Hospital Neuroscience Foundation)