Anticonvulsant action of 2-chloroadenosine injected focally into the inferior colliculus and substantia nigra

Focal injection of 2-chloroadenosine into the substantia nigra protects Sprague-Dawley rats against electroshock seizures (50 mA. 60 Hz, 0.2 s) and genetically epilepsy prone rats against audiogenic seizures. 2-Chloroadenosine infusion into the substantia nigra pars reticulata provided significant protection against electroshock seizures (1.66, 8.33 and 25 nmol) and audiogenic seizures (66, 331 pmol and 1.66 nmol). High doses of 2-chloroadenosine injected into the substantia nigra pars compacta resulted in a similar suppression of electroshock seizure activity (8.33 nmol) and audiogenic seizures (1.66 nmol). No anticonvulsant activity was observed when 2-chloroadenosine was infused into the entopeduncolar nucleus. Lower doses of 2-chloroadenosine provided significant protection against audiogenic seizures (66 and 331 pmol) when injected into the inferior colliculus. Aminophylline antagonised these effects, indicating that purinergic mechanisms are involved in both audiogenic and electroshock seizures. In addition, the similarity of these effects to those elicited by excitatory amino acid antagonists in the inferior colliculus and substantia nigra pars reticulata is consistent with 2-chloroadenosine acting by reducing excitatory transmission.