2-Chloro-N-6-cyclopentyladenosine-elicited attenuation of evoked glutamaterelease is not sufficient to give complete protection against pilocarpine-induced seizures in rats

The effects of 2-chloro-N-6-cyclopentyladenosine (CCPA) perfused intrahippo campally (1 muM) and injected intraperitoneally (0.5 mg/kg) were investigat ed in focally-evoked pilocarpine-induced (10 mM) seizures in freely moving rats. While the intrahippocampal perfusion of this highly selective adenosi ne A(1) receptor agonist gave complete protection against pilocarpine-induc ed seizures, systemic administration only partially protected the animals, as evaluated by concomitant behavioural and electrocorticographical (ECoG) observations and monitoring of the neurotransmitter alterations. However, p ilocarpine-evoked elevation of hippocampal glutamate overflow was significa ntly attenuated by CCPA irrespective of the mode of administration. Acute p retreatment with systemic 8-cyclopentyl-1,3-dipropylxanthine,a selective A( 1) antagonist, reversed both the partial protective effect and the attenuat ing effect on the extracellular glutamate elicited by systemic CCPA adminis tration. Intrahippocampal CCPA markedly reduced basal hippocampal dopamine efflux but not GABA or glutamate and considerably attenuated the pilocarpin e-evoked elevation in dopamine levels. Systemic CCPA appeared to have littl e influence on the overall pattern of dopamine elevation. The findings give evidence that CCPA-elicited abatement of the evoked glutamate release alon e, cannot fully account for its anticonvulsant effect and may suggest that the effects mediated by adenosine on postsynaptic adenosine receptors could be more crucial for its anticonvulsant effect. (C) 2001 Elsevier Science L td. All rights reserved.