Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the...

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.