Effects of enadoline on the development of pentylenetetrazol kindling, learning performance, and hippocampal morphology

Opioids are involved in the development of epileptic seizures. Recently, in terest has been focused on the role of the kappa-opioid receptor agonists a s novel approaches to the treatment of epilepsy. Tn the present study we in vestigated the effects of the kappa-opioid receptor agonist enadoline (Ena) on pentylenetetrazol (PTZ) induced seizures, PTZ kindling, shuttle-box per formance and hippocampal neuromorphology. Ena injected i.c.v. in doses of 1 and 10 nmol did not affect acute PTZ seizures. In the course of PTZ kindli ng development, co-treatment (I nmol) with the kappa-opioid receptor agonis t suppressed seizure strength. Eight days after kindling completion the ani mals received a challenge dose of PTZ. In reaction to challenge, kindled an imals which were pretreated with Ena reached significantly lower seizure sc ores. Kindling resulted in diminished shuttle-box performance. Learning per formance in kindled animals pretreated with Ena was not normalised. Kindlin g resulted in increased glutamate binding. Interestingly, in comparison wit h the saline/saline group, neither in the Ena/saline nor in the Ena/PTZ tre ated groups changes in glutamate binding were found. That means that Ena pr evented the increase in glutamate binding in the kindled group. In kindled animals significant cell loss in CA1 of the dorsal hippocampus was found an d this was efficaciously counteracted by Ena. However, Ena alone did induce similar cell loss compared to kindled animals. It is hypothesised that the effects of enadoline are mainly due to interferences with glutamatergic sy stems. (C) 1999 Elsevier Science B.V. All rights reserved.