SCH 23390 affords protection against soman-evoked seizures in the freely moving guinea-pig: a concomitant neurochemical, electrophysiological and behavioural study.
We studied the role of striatal dopamine (DA) release in seizure activity evoked by the subcutaneous administration of the cholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman), in the guinea-pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the D(1)-like receptor antagonist SCH 23390 (0.5 mg kg(-1)) or the D(2)-like receptor antagonist sulpiride (30 mg kg(-1)). Microdialysis and HPLC with electrochemical detection were used to monitor changes in extracellular levels of striatal DA and its metabolites, acetylcholine and choline. These data were correlated with changes in the striatal and cortical electroencephalogram and observation of predefined clinical signs. We found that the blockade of the D(1) receptor with SCH 23390 can inhibit seizure activity, while blockade of the D(2) receptor with sulpiride can augment the evoked seizure activity. These results clarify the involvement of the dopaminergic system in soman-evoked seizures.
Bourne
J A
JA
Biomedical Sciences Department, CBD Porton Down, Salisbury SP4 0JQ, UK. james.bourne@med.monash.edu.au
Fosbraey
P
P
Halliday
J
J
D000818:Animals; D001286:Atropine Derivatives / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004569:Electroencephalography; D006168:Guinea Pigs; D017551:Microdialysis; D017447:Receptors, Dopamine D1 / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012999:Soman; D013469:Sulpiride / Q000494:pharmacology
D001286:Atropine Derivatives; D001552:Benzazepines; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D013469:Sulpiride; C006649:methylatropine; D012999:Soman