INCREASE IN THE CONTENT OF ADENOSINE 3'5'- MONOPHOSPHATE IN MOUSE FOREBRAIN DURING SEIZURES AND PREVENTION OF THE INCREASE BY METHYLXANTHINES

Abstract— Seizures produced significant elevations of the content of adenosine 3',5'-monosphosphate (cyclic AMP) in mouse forebrain in vivo. The content of cyclic AMP doubled at 5 s and had increased four- to five-fold at 90 s after the onset of tonus. Smaller increases were observed when mice were placed in an 0₂-enriched atmosphere. The increase in the content in forebrain of cyclic AMP during seizures was significantly reduced in mice that had previously been injected with heophylline or caffeine. The methylxanthines did not alter the initial (pre-ictal) level of cycIicXMP in mouse forebrain. On the basis of these and previous data, the following hypothesis is proposed to account for the present observations : When seizures produce asphyxia in the forebrain, the consequent dephosphorylation of adenine nucleotides liberates small amounts of free adenosine which may then diffuse out of cells and activate an adenyl cyclase-linked receptor that is located on plasma membranes and is accessible from the extracellular space.