Is the anticonvulsant effect of substantia nigra infusion of gamma-vinyl-GABA (GVG) mediated by the GABAA receptor in rat pups?
The substantia nigra GABAergic system is considered important for the modification of seizures. Our previous studies have shown that, in rat pups, nigral infusions of baclofen suppressed flurothyl-induced seizures. In the present study, we determined, in rat pups, the effect of nigral infusions of gamma-vinyl-GABA (GVG) on clonic-tonic seizures induced by flurothyl, generated a dose-response curve of the GVG effect and investigated the possible role of the nigral GABAA receptor in mediating the GVG effect. Bilateral nigral infusions of GVG profoundly suppressed flurothyl-induced tonic seizures in a dose-dependent fashion. Flurothyl-induced clonic seizures were not modified. The lowest effective dose of nigral GVG administration was 5 micrograms/0.25 microliter per site. Nigral infusions of GVG at doses greater than 10 micrograms/0.25 microliter induced sedation as well. Infusions of GVG, 2 mm dorsal to the substantia nigra, did not alter seizure latencies. Bilateral nigral infusions of bicuculline, a specific GABAA receptor antagonist, reduced the protective potency of GVG against flurothyl-induced seizures. Nigrally administered muscimol, a GABAA receptor agonist, also attenuated the anticonvulsant effect of GVG. These findings suggest that the optimal dose of nigrally infused GVG against flurothyl-induced seizures is in the range of 5-10 micrograms/0.25 microliter and that GVG may be more efficient as an anticonvulsant for the treatment of tonic seizures in developing animals. The anticonvulsant effect of GVG may, in part, involve the nigral GABAA receptor. The data, together with the previous experiments, indicate that both nigral GABAA and GABAB receptors may play a role in the regulation of seizures in rat pups.(ABSTRACT TRUNCATED AT 250 WORDS)
Xu
S G
SG
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Sperber
E F
EF
Moshé
S L
SL
D000614:Aminocaproates / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism*; D001640:Bicuculline / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*; D020888:Vigabatrin
D000614:Aminocaproates; D000927:Anticonvulsants; D011963:Receptors, GABA-A; D009118:Muscimol; D020888:Vigabatrin; D001640:Bicuculline