BLOCK BY N-6-L-PHENYLISOPROPYL-ADENOSINE OF THE ELECTROPHYSIOLOGICAL AND MORPHOLOGICAL CORRELATES OF HIPPOCAMPAL ISCHEMIC-INJURY IN THE GERBIL

1 The effects of the mixed A(1) and A(2) adenosine receptor agonist N- 6-L-phenyl-isopropyladenosine (L-PIA) were tested on ischaemia-induced hippocampal neuronal injury in gerbils subjected to 5-min bilateral c arotid occlusion. For comparison, the effects of the selective A(2) ad enosine receptor agonist, CGS 21680 were tested. 2 Five-min bilateral carotid occlusion produced within 1 week an irreversible suppression o f the CA1, but not of the dentate extracellular electrical somatic res ponses, in 30% of gerbil hippocampal slices with respect to controls. In addition, a significant reduction occurred in the density of CA1 hi ppocampal pyramidal neurones but not of dentate granule cells with res pect to controls. 3 Injection 1 h before or after bilateral carotid oc clusion of L-PIA (0.8-1.5 mg kg(-1), i.p.) but not of CGS 21680 (5 mg kg(-1), i.p.), significantly prevented the irreversible disappearance of the CA1 extracellular electrical somatic responses with respect to controls. In addition, the CA1 pyramidal neuronal loss was also preven ted. 4 The results show that activation of A(1) adenosine receptors is able to prevent or block the electrophysiological and morphological c orrelates of hippocampal neuronal injury after global ischaemia in the gerbil, suggesting that adenosine receptor agonists might have a usef ul role in the treatment of neuronal functional and anatomical injury due to ischaemia.