Brain tissue hydrolysate acts on presynaptic adenosine receptors in the rat hippocampus

Adenosine is a potent inhibitory modulator in the brain. It suppresses glutamatergic synaptic transmission and possibly acts as a brain endogenous neuroprotective agent. In this study we have examined the effects of a clinically used porcine brain tissue hydrolysate, Cerebrolysin, on synaptic transmission in the CA1 area of rat hippocampal slices. A major effect of the drug at doses approximating those administered clinically to demented patients was a depression of synaptic transmission at the Schaffer collateral-commissural pathway in CA1. Detailed analysis showed that the inhibition is presynaptic and can be reduced by low doses of a specific blocker of adenosine A1 receptors, 8-cyclopentyltheophylline. Because Cerebrolysin does not contain a detectable amount of adenosine, the effect on adenosine A1 receptors must be indirect, perhaps by release of the endogenous agonist. This action of Cerebrolysin is consistent with a putative neuroprotective action underlying its clinical usage.