Cerebellar cyclic nucleotides and the development of convulsion, with reference to the anticonvulsant activity of diazepam.
Dibutyryl cyclic GMP (DbcGMP) or dibutyryl cyclic AMP (DbcAMP) given to rats intracerebellarly in a dose of 200 nmol/head produced electroencephalographic convulsive changes. Intracerebellar (i.c.) administration of lower doses (100 nmol/head) of DbcGMP and DbcAMP and 200 nmol/head of norepinephrine (NE) and glutamate (Glu) facilitated the pentylenetetrazol (PTZ)-induced convulsions. Diazepam (100 nmol/head, i.c.) suppressed the PTZ-induced convulsions. GABA (400 nmol/head, i.c.) did not affect the PTZ-induced convulsions. These results suggest that DbcGMP, DbcAMP and Glu inhibit seizure control mechanisms in the cerebellum, and that one of the sites of the anticonvulsant action of diazepam is located in the cerebellum.
D000818:Animals; D000927:Anticonvulsants; D003994:Bucladesine / Q000494:pharmacology; D002531:Cerebellum / Q000187:drug effects / Q000503:physiopathology*; D003975:Diazepam / Q000494:pharmacology*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D008297:Male; D009712:Nucleotides, Cyclic / Q000502:physiology*; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000927:Anticonvulsants; D009712:Nucleotides, Cyclic; D003995:Dibutyryl Cyclic GMP; D005680:gamma-Aminobutyric Acid; D003994:Bucladesine; D003975:Diazepam; D010433:Pentylenetetrazole