Motor alterations and neuronal damage induced by interacerebral administration of ruthenium red - Effect of NMDA receptor antagonists and other anticonvulsant drugs

The effects of the intracerebroventricular (icv) and the intrahippocampal (ih) microinjection of the inorganic dye Ruthenium red (RuR) on motor activity, and the protective action of excitatory amino acid receptor antagonists and of GABAergic drugs, were studied in the rat. When administered icy, RuR produced intense tonic-clonic convulsions which were refractory to N-methyl-D-aspartate (NMDA) receptor antagonists and to diphenylhydantoin, whereas aminooxyacetic acid (AOA) and valproate only partially protected against seizure activity. The most notable motor effect of the ih RuR administration was the appearance of intense wet-dog shakes (WDS) behavior, which was remarkably attenuated by the icy or intraperitoneal (ip) administration of the NMDA receptor antagonists (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonoic acid (CPP), CGP-37849, and MK-801, but not by their ih coinjection with RuR. Systemic AOA and valproate were also effective in reducing the number of WDS, whereas the non-NMDA receptor antagonist CNQX was ineffective. Light and electron microscopic observations of the RuR-injected brains revealed that the dye was highly concentrated in neuronal somas located in or near the injected areas. In the case of the CA1 region, remarkable damage of the pyramidal neurons was manifested by vacuolization, and 5-9 d after the injection notable cell loss and disruption of the CA1 cell layer organization was apparent. The results indicate that RuR penetrates selectively neuronal bodies and damage them, and suggest that the resulting motor alterations involve hyperactivity of glutamatergic neurotransmission.