Injection of benzodiazepines but not GABA or muscimol into pars reticulata substantia nigra suppresses pentylenetetrazol seizures.
The substantia nigra pars reticulata (SNpr), a brain area rich in GABA and benzodiazepine receptors, is thought to be involved in the regulation of seizure activity. It has been shown to be a site of anticonvulsant action of substances that affect GABA transmission. The anti-pentylenetetrazol (PTZ) activities of intranigral of muscimol, a GABAA receptor agonist; two benzodiazepines, midazolam and flurazepam; and GABA were examined. Microinjection of a wide dose range of both GABA and muscimol into the SNpr failed to show anti-PTZ seizure activity. Intranigral injections of midazolam and flurazepam showed clear, dose-dependent anti-PTZ effects. Ro15-1788, a benzodiazepine receptor antagonist, reversed the anticonvulsant effects of midazolam when both were infused intranigrally. Intranigral infusion of muscimol or flurazepam protected rats from bicuculline-induced tonic seizures. The results suggest that the anti-PTZ effects of benzodiazepines in SNpr might not be mediated through GABAA receptors. Another possibility is that nigral neurons bearing GABAA receptors functionally linked to benzodiazepine sites may not be representative of the whole population of nigral neurons inhibited by GABA agonists. This could result in different patterns of inhibition of nigral efferent activity by GABAA agonists and benzodiazepines.
Zhang
H
H
Department of Pharmacology, Medical College of Ohio, Toledo 43699.
Rosenberg
H C
HC
Tietz
E I
EI
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D005479:Flurazepam / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D009118:Muscimol / Q000494:pharmacology*; D010433:Pentylenetetrazole; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D001569:Benzodiazepines; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005479:Flurazepam; D008874:Midazolam; D010433:Pentylenetetrazole