Morphological alterations of neurons and astrocytes and changes in emotional behavior in pentylenetetrazol-kindled rats.

Changes of emotional behavior and neuronal cell loss in the hippocampus were investigated after pentylenetetrazol (PTZ) induced kindling in rats. Behavioral and morphological changes were studied in partially and fully kindled rats and after different postkindling periods comparing to the controls. The resident-intruder test indicated a diminished offensive behavior in partially and fully kindled animals. The open-field and the cat-odor exposition tests reveal changes in defensive behavioral pattern only in fully kindled rats. A decrease of exploratory locomotion and an increase in freezing were assessed in the open-field and the cat-odor exposition test, respectively, up to 10 weeks after the end of kindling. The first damaged neurons (CA4 region) were observed in the partially kindled group (PK), correlating with an increase in the glial fibrillary acidic protein (GFAP)-immunoreactivity (GFAP-IR) and hypertrophy of astrocytes. The most significant increase in the number of damaged neurons was detected 24 h after completion of kindling (selective vulnerability: CA4/CA1>DG>CA2+CA3). The neuronal loss went on for 10 weeks postkindling. A low correlation between the number of Stage 4 kindling seizures and the number of damaged hippocampal neurons was found 24 h after the end of kindling in individual rats. The present results demonstrate that PTZ kindling goes along with long-lasting changes in emotional behavior. The alterations of the defensive behavior after the termination of kindling can be interpreted as depression-like and are obviously associated with a characteristic pattern of neuronal loss in various hippocampal regions.