In pharmacokinetic study, rats were administered 5.0 mg/kg intravenously

Rat hippocampal slices (400 micro-m thick) were submerged in a brain slice recording chamber immersed flowing ACSF (32 deg-C, 3-4 mL/min). Stimulus-evoked population spikes and field e.p.s.p.'s were recorded with electrodes in the stratum pyramidale and stratum radiatum area of CA1, respectively. Songorine stock was dissolved in DMSO at a concentration of 1 mM. Experimental concentrations between 1 - 100 micro-M were prepared by dilution with ACSF. At concentrations between 10 -100 micro-M songorine induced a concentration-dependent increase in the amplitude of the orthodromic population spike and of the field e.p.s.p. The effect was not reversed by 90 min of washout. However, Songorine did not affect the size and shape of the presynaptic fiber spike indicating that the enhancement of the synaptic response is not a consequence of increased afferent excitability. The antidromically evoked population spike was no affected by songorine at concentrations up to 100 micro-M 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. The inclusion of the NMDA receptor antagonist (D-AP5) did not alter the effects of songorine. However, both dopamine D2 receptor antagonists Sulpride (0.1 micro-M) and Haloperidol (10 micro M) abolished the songorine effect. The effects of Songorine were closely mimicked by the dopamine releaser, amantadine (100 mM). Finally, the effects of songorine were unaltered by the inclusion of the selective D1 receptor antagonist, SCH23390. These results suggest that songorine enhances excitatory synaptic transmission which may be due to an agonist action at D2 receptors.