THE PROTECTIVE EFFECT OF 2-CHLOROADENOSINE AGAINST THE DEVELOPMENT OFAMYGDALA KINDLING AND ON AMYGDALA-KINDLED SEIZURES

The influence of 2-chloroadenosine, a non-metabolizable adenosine A(1) receptor agonist, was tested on the development of electrically kindl ed amygdala and on the seizure responses of fully kindled rats. Focal intra-amygdaloid injection of 2-chloroadenosine (1-10 nmol/0.5 mu l) 2 0 min before applying the daily kindling stimulus prevented the develo pment of the kindling process. The behavioural seizure score and the a fterdischarge duration were reduced below their initial values. The an tiepileptogenic effects of 1 and 10 nmol of 2-chloroadenosine were rev ersible 8-10 days after withdrawal of the drug. When 2-chloroadenosine was tested on fully developed stage 5 amygdala-kindled seizures, it i ncreased the generalised seizure threshold in a dose-dependent manner. A maximum efficiency of 125% (P <0.001) was achieved with 5 nmol and the median effective dose was 0.55 nmol. Higher doses resulted in the reduced anticonvulsant effect (P <0.05). With the same daily stimulati on, 2-chloroadenosine 5 nmol in 0.5 mu l vehicle, significantly reduce d the maximum seizure score by 90%, the afterdischarge duration by 88% and completely blocked the generalised seizure duration. The antiseiz ure activity of the drug lasted for 3 days. In conclusion, 2-chloroade nosine not only acts as an anticonvulsant against electrically induced kindled seizures as described here, and against audiogenic seizures, electroshock and a variety of chemical convulsants as described by oth ers, it prevents the development of the epileptic state by kindling-st imulation, i.e., it is antiepileptogenic. We theorise here that this i s due to its blockade of presynaptic glutamate release.