VASOPRESSIN MESSENGER-RNA CHANGES DURING KINDLING - THE EFFECTS OF KINDLING SITE AND STAGE

Because of the many anatomical and functional links to the limbic syst em, the neuroendocrine system is often affected by limbic disturbances . Limbic seizures in humans and animals alter neuroendocrine function and hormone levels. We have shown that in an animal model for partial seizures, the amygdala kindred rat, plasma vasopressin levels are elev ated and a sustained increase in vasopressin (VP) mRNA follows stage 5 kindled seizures. In the present experiments we sought to determine w hen during the course of amygdala kindling the VP mRNA increase occurs and whether specific anatomical pathways mediate this increase. Anima ls kindled to early seizure stages (stages 1, 2 or 3) had no consisten t increase in VP mRNA in the supraoptic nucleus (SON) while animals ki ndled to generalized seizures, stages 4 or 5, invariably had increased VP mRNA relative to controls. Electrical kindling to stage 5 seizures from two other brain sites, the dorsal hippocampus and the anterior o lfactory nucleus, consistently resulted in a significant increase in V P mRNA one week after completing kindling. In air experiments the incr ease in VP mRNA in the SON showed no differences related to the side o r proximity of the electrodes used for kindling. Measures of water bal ance did not change following kindling. These results indicate that ki ndred seizure generalization is a prerequisite for the long-term incre ase in VP mRNA. Furthermore, the VP mRNA increase appears to involve p olysynaptic pathways accessible from different limbic kindling sites. These studies support the hypothesis that changes in mRNA regulation m ay contribute to the neuroendocrine pathophysiology accompanying limbi c seizures.