Anticonvulsant actions and interaction of GABA agonists and a benzodiazepine in pars reticulata of substantia nigra.
In a previous study, infusion of flurazepam and midazolam, but not GABA or muscimol into the pars reticulata of substantia nigra (SNpr), blocked the tonus induced by a high dose of pentylenetetrazol (PTZ). It was hypothesized that the divergence of GABAA agonist and benzodiazepine (BZ) actions might be due to a complex action of the GABAA agonists in SNpr that is not shared by the BZs, and which is specific for certain experimental seizures. This was tested in the present study in which GABA, muscimol, midazolam, and combinations of midazolam with GABA and with muscimol were tested against seizures induced by PTZ (40 or 100 mg/kg, i.p.), bicuculline (0.5 mg/kg, i.v.) and maximal electroshock (MES). Intranigral midazolam was effective against PTZ, bicuculline and MES seizures. Intranigral GABA or muscimol, infused together with midazolam, prevented midazolam from blocking tonus induced by the high dose of PTZ. For bicuculline seizures, midazolam alone had a better overall anticonvulsant effect than did the combination of midazolam plus muscimol. Intranigral muscimol, midazolam and a combination of two were equally effective against the low dose PTZ (40 mg/kg, i.p.) and MES seizures. Since the effect of intranigral drugs was model-specific, it was suggested that different populations of nigral output neurons were involved in regulating the generalization of these seizures.
Zhang
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Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Rosenberg
H C
HC
Tietz
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EI
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D001640:Bicuculline; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007267:Injections; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology*; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D013378:Substantia Nigra / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000927:Anticonvulsants; D001569:Benzodiazepines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D008874:Midazolam; D010433:Pentylenetetrazole; D001640:Bicuculline