Susceptibility to pentylenetetrazol-induced and audiogenic seizures in rats with selective fimbria-fornix lesions and intrahippocampal septal grafts

Abstract

At the age of 31 days, Long-Evans female rats received electrolytic lesions either of the medial fimbria ( N = 24), of the dorsal subcallosal fornix ( N = 24), or of both structures ( N = 24). Ten rats were used as sham-operated controls. Ten days later, half the rats of each lesion group received intrahippocampal grafts of acetylcholinerich fetal basal forebrain cell suspensions. Twelve months after grafting, all surviving rats, except six grafted rats which became very difficult to handle (because they developed convulsive behavior) were tested for reactivity to pentylenetetrazol (30 mg/kg, i.p.) and to sound (120 dB, 90 s). Grafted rats were found to be more reactive to the drug and less reactive to sound than their nongrafted counterparts with similar lesions. Reactivity to pentylenetetrazol of grafted rats was correlated with body weight and extent of graft-induced hippocampal damage, but not with graft size. Reactivity to sound, which was apparently not dependent on hippocampal damage or graft size, might be related to enhanced graft-derived cholinergic activity in the hippocampus. Our results show that intrahippocampal septal grafts interfere in opposite directions with the seizure-inducing treatments used, so that it can be assumed that the physiologic mechanisms by which grafts do so and by which these treatments induce seizures are likely to be different.