Effects of the Aconitum alkaloid songorine on synaptic transmission and paired-pulse facilitation of CA1 pyramidal cells in rat hippocampal slices.

1. The present study investigated the electrophysiological effects of songorine (1 100 microM), an alkaloid occurring in plants of the Aconitum genus, in rat hippocampal slices. 2. Songorine (10-100 microM) evoked a concentration-dependent increase in the amplitude of the orthodromic population spike and in the slope of the field e.p.s.p. The enhancement was long-lasting and was not reversed by up to 90 min of washout. Songorine failed to affect size and shape of the presynaptic fiber spike which represents the compound action potential of the Schaffer collaterals. This indicates that enhancement of the synaptic response is no consequence of an increased afferent excitability. 3. The antidromically evoked population spike was not affected by songorine at concentrations up to 100 microM suggesting that the enhancement of the orthodromic population spike and of the field e.p.s.p. was not due to an increase in pyramidal cell excitability. 4 The input-output curve for the postsynaptic population spike was shifted to the left implying that a presynaptic fiber spike of the same size elicited a larger postsynaptic response, indicating a decrease in threshold for generation of the population spike. 5. The songorine-evoked increase in excitability was not affected by the NMDA receptor antagonist, D-AP5. However, the effect of songorine was completely abolished by the selective dopamine D2 receptor antagonist sulpiride (0.1 microM) as well as by haloperidol (10 microM) and was mimicked by application of the dopamine releaser, amantadine (100 mM). In contrast, the selective D1 receptor antagonist, SCH23390, did not block the action of songorine. 6. The results indicate that the plant alkaloid songorine enhances excitatory synaptic transmission which may be due to an agonistic action at D2 receptors.