Antiepileptic effects of NPY on pentylenetetrazole seizures

Intracerebroventricular (i.c.v.) administration of NPY inhibits limbic seizure activity induced by kainic acid or electrical hippocampal stimulation in vivo. Similarly, antiepileptiform effects have been demonstrated in hippocampal slice models. This suggests a possible antiepileptic potential of NPYergic agonists in future treatment of complex partial seizures in humans. To further characterize the antiepileptic potential of NPY, the effects of NPY administered i.c.v. were studied on seizures induced by subcutaneous injection of pentylenetetrazole (PTZ), a widely used antiepileptic screening test believed to model generalized myoclonic seizures. NPY significantly and dose-dependently inhibited PTZ-induced clonic seizures as revealed by increases in seizure latencies. In addition, NPY caused an overall significant reduction in the number of rats developing tonic seizures and in mortality following PTZ, indicating that NPY also reduces seizure severity. By demonstrating antiepileptic activity of NPY in yet another seizure model, this study further adds to the concept of NPY receptors as potentially novel targets in future treatment of seizure disorders. Specifically, antiepileptic effects in the PTZ model suggest that NPYergic agonists might also prove active against human myoclonic seizures. (C) 1998 Elsevier Science B.V. All rights reserved.