Hypothermia inhibits pentylenetetrazol kindling and prevents kindling-induced deficit in shuttle-box avoidance

In this study, we evaluated the effects of hypothermic exposure on pentylenetetrazol (PTZ) kindling and the resulting deficit of shuttle-box avoidance learning in rats. Additionally, to acknowledge neuronal cell loss, we estimated the number of toluidine blue-positive cells in different brain regions after PTZ kindling and hypothermia exposure in comparison to different normothermic and hypothermic controls. To obtain hypothermic conditions over a period of up to about 3 h, 30 min after PTZ application the animals were treated with 5 mg/kg chlorpromazine (CP) and 25 min later exposed to 15 degrees C cold water for 5 min. Under these conditions the rectal and the striatal temperature were reduced up to a maximum of 5 degrees C. The additional injection of CP did not influence the development of PTZ kindling. Animals treated with PTZ/CP and exposed to hypothermia did not reach the criterion for kindling. Furthermore, this group of animals did not demonstrate any learning deficit. Forty-eight hours after the last kindling application the number of toluidine blue-stained cells was decreased in the investigated brain regions (hippocampal CA1 and CA3 sector, hilus, and cingular cortex) of kindled rats. Hypothermia protected from cell damage in the hippocampal CA3 sector and in the hilus. Results suggest that the inhibiting effect of hypothermia on the development of kindling and the following learning deficit possibly resulted from the suppression of cell damage in distinct brain structures on PTZ-kindled rats.