Sudden cooling of the isolated spinal cord of frogs results in characteristic seizure-like activity in the hind legs. In the present investigation, these spinal seizures induced by sudden cooling (SSSC) were studied to determine whether excitatory amino acids (EAAs) are involved in the mediation of this activity. The nonspecific EAA antagonist, l-glutamic acid diethyl ester and cis-2,3-piperidine dicarboxylic acid inhibited the clonic and tonic phase of SSSC after intralymphatic or intrathecal administration. The antagonist-γ-d-glutamylaminomethylsulfonic acid and γ-d-glutamyltaurine also suppressed both phases after intrathecal injections. The NMDA receptor antagonist dl-2-amino-5-phosphonovaleric acid, dl-2-amino-7-phosphonoheptanoic acid, and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid were effective inhibitors of the tonic phase and actually prolonged the duration of the clonic phase, an effect similar to that observed after low doses of γ-d-glutamylglycine. SSSC were resistant to spinal perfusion to tetrodotoxin (1 μM). The concentrations of glutamate, aspartate, and glycine were increased in the Ringer's solution surrounding rapidly cooled spinal cord slices, but only in cords from species that elicited some magnitude of SSSC, not in cords from species resistant to induction of SSSC. Our data support the hypothesis that EAAs play a role in SSSC via activation of quisqualate receptors.
Bibliographical noteFunding Information:
The authors gratefully acknowledge the competent assistance of Dr. Berta E. Martinez in the performance of these experiments and Dr. Stephen R. Skilling and Dr. David H. Smullin for their help and advice during the HPLC analyses. Travel to the United States and research expenses were supported in part by the International Training Program for Middle Income Countries of the U.S. Department of Agriculture (for N.L.D.) and by National Institute on Drug Abuse Grants DA-04090, DA-04190, and DA-00124 to A.A.L.