The anti-ischaemic drug, eliprodil, blocks hyperactivity induced by intra-accumbens injection of spermine.
NMDA receptor mechanisms in the nucleus accumbens play an important role in the control of locomotor activity. Among the several binding sites associated with these receptors, the polyamine-sensitive sites have received relatively little attention. It has recently been shown, however, that the anti-ischaemic drug eliprodil NMDA antagonist effects probably mediated by activity at this polyamine site. In the present series of experiments the effects of injections of spermine and eliprodil into the nucleus accumbens of rats were investigated. Locomotor hyperactivity was produced by intra-accumbens injection of spermine, phencyclidine and AP7. Phencyclidine, but not AP7, produced a similar effect after systemic injection. Eliprodil did not increase locomotion after either intra-accumbens or i.p. administration. However, systemic injection of eliprodil (5, 10, 20mg/kg) produced a dose-related antagonism of hyperactivity induced by intra-accumbens spermine, but not by systemic or intra-accumbens injection of d-amphetamine. These results provide the first behavioural demonstration of the polyamine antagonist properties of eliprodil, and further emphasise the differences between the pharmacological profile of eliprodil and those of other NMDA antagonists.
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D.J.
DJ
Sanger
G.
G
Perrault
E.
E
Audi