Exposure of hippocampal slices to quisqualate sensitizes synaptic responses to phosphonate-containing analogues of glutamate.

Exposure of transverse slices of rat hippocampus to quisqualate (Quis) resulted in a marked increase in the potency of D- and L-2-amino-4-phosphonobutanoate (APB) and D- and L-2-amino-5-phosphonopentanoate (APV) for depression of extracellular synaptic field potentials recorded from CA1 pyramidal cells. L-APB depressed the amplitude of CA1 field potentials with an IC50 = 1800 microM before exposure to Quis. After a brief (4 min) exposure to sufficient Quis (16 microM) to depress the response by 50%, L-APB depressed these responses with an IC50 = 54 microM. These phosphonate-containing glutamate analogues transiently induced population-spiking after the tissue was pretreated with Quis. This suggests that APB and APV can act as agonists at micromolar concentrations.