Vasopressin mRNA changes during kindling: the effects of kindling site and stage

Because of the many anatomical and functional links to the limbic system, 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 kindled rat, plasma vasopressin levels are elevated and a sustained increase in vasopressin (VP) mRNA follows stage 5 kindled seizures. In the present experiments we sought to determine when during the course of amygdala kindling the VP mRNA increase occurs and whether specific anatomical pathways mediate this increase. Animals kindled to early seizure stages (stages 1, 2 or 3) had no consistent increase in VP mRNA in the supraoptic nucleus (SON) while animals kindled 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 olfactory nucleus, consistently resulted in a significant increase in VP mRNA one week after completing kindling. In all experiments the increase in VP mRNA in the SON showed no differences related to the side or proximity of the electrodes used for kindling. Measures of water balance did not change following kindling. These results indicate that kindled seizure generalization is a prerequisite for the long-term increase in VP mRNA. Furthermore, the VP mRNA increase appears to involve polysynaptic pathways accessible from different limbic kindling sites. These studies support the hypothesis that changes in mRNA regulation may contribute to the neuroendocrine pathophysiology accompanying limbic seizures.