Involvement of D₁ dopamine receptor mechanism in ischemia-induced impairment of CA1 presynaptic fiber spikes in rat hippocampal slices

The effect of dopamine (DA) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collateral were investigated using hippocampal slices. Treatment with D₁ dopamine receptor antagonist, SCH23390 produced a concentration-dependent attenuation of the ischemia-induced decrease of presynaptic potentials. The magnitude of recovery of the CA1 presynaptic potential in SCH23390-treated slices at 10 and 100 μM was 28 and 54%, respectively. Whereas, treatment with D1 dopamine receptor agonist, SKF38393 exacerbated the ischemia-induced decrease in the CA1 presynaptic potential. The decrease of CA1 presynaptic potential by ischemia was affected by neither D₂ dopamine receptor agonist, bromocriptin and quinpirole nor D₂ dopamine receptor antagonist, sulpiride. The neuroprotective effect of SCH23390 was completely blocked by cotreatment with SKF38393. The present results demonstrated that the blockade of D₁ dopamine receptor function played a neuroprotective role in ischemic damage, suggesting a facilitatory role of D₁ dopamine receptor-operated function in ischemia-induced neuronal deficits.