Blockade of GABA receptors in superior colliculus protects against focally evoked limbic motor seizures.
Blockade of GABA receptors in the rat superior colliculus (SC) has been shown to protect against maximal electroshock-induced tonic convulsions and spontaneous generalized non-convulsive seizures. In the present study, we determined that blockade of GABA receptors in SC could also protect against focally evoked limbic motor seizures. Limbic motor seizures were induced by the unilateral focal application of bicuculline methiodide into area tempestas (AT), an epileptogenic site in the deep prepiriform cortex. Control rats (receiving bilateral infusions of saline into SC) all exhibited convulsive seizures following bicuculline in AT. Rats pretreated (5 min before) with bicuculline (50 pmol) bilaterally in the deep layers of the SC, were protected against the AT-evoked convulsive seizures. Unilateral application of bicuculline in the deep SC or bilateral application in the superficial layers of the SC did not alter the convulsive response to bicuculline in AT. These results indicate that the anticonvulsant action of GABA blockade in SC is not limited to tonic convulsive seizures but extends to the clonic manifestations evoked by seizures originating in forebrain limbic circuits. Given that the deep layers of SC receive inputs from GABA neurons in substantia nigra and that suppression of the activity of nigral neurons is anticonvulsant against a variety of seizures (including those evoked from AT), it is likely that the anticonvulsant action of bicuculline in SC is due to interference with the influence of a nigrotectal GABAergic projection.
Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20007.
K
K
Gale
A
A
Pazos
R
R
Maggio
K
K
Japikse
P
P
Pritchard
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004597:Electroshock; D004828:Epilepsies, Partial / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D058787:GABA-A Receptor Antagonists; D008032:Limbic System / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013477:Superior Colliculi / Q000187:drug effects / Q000502:physiology*
D058787:GABA-A Receptor Antagonists; C017069:bicuculline methiodide; D001640:Bicuculline