[Cholera toxin induced epileptogenic focus--special reference to cyclic AMP metabolism and epileptogenic focus (author's transl)].

Epilepsy-like convulsive seizures have been induced by cholera toxin administration into the rat amygdaloid complex. Between the 8th and 48th hr after the administration, rhythmic spike discharges (1--3 spikes/sec) were electroencephalographically observed bilaterally in the amygdaloid complexes, and rats exhibited abnormal behaviors such as running, jumping, tail lifting, rearing, vocalization aggressive behavior, facial twitching and increased salivation. During these stages, high voltage spikes were intermittently observed with generalized convulsive seizures. Duration of the seizure was 1--2 min and the incidence was 0--6 times/hr. At 48 hrs after the administration or thereafter, convulsive seizures disappeared and electroencephalographic abnormalities were gradually normalized. Occasional rhythmic spike discharges, however, were observed more than 168 hrs after the administration. Since autoradiographic observations with 125I-labeled cholera toxin revealed that the injected toxin does not spread out at all from the injected site, the use of this toxin seems to be an ideal procedure to produce micro-epileptogenic foci. Cyclic AMP content as well as adenylate cyclase activity in the ipsilateral amygdaloid complex was significantly increased during preconvulsive and convulsive states. The administration of 5 x 10(-8) moles of dibutyryl cyclic AMP through the cannula implanted into the amygdaloid complex also induced behavioral and electroencephalographic abnormalities similar to those found in the cholera toxin-treated animals. These results suggest that cyclic AMP and/or cyclic AMP dependent neuronal mechanisms may play a significant role in the establishment of epileptogenic focus. Possible use of this animal model for the study of anti-epileptic drugs are also suggested.