Electroconvulsive shock increases interstitial concentrations of uric acid in the rat brain.
This study examined the effects of electroconvulsive shock (ECS) on striatal interstitial concentrations of the purine metabolite uric acid (UA) using microdialysis in freely moving rats. UA increased to about 200% of baseline following ECS. Intense seizure activity induced by the convulsant agent flurothyl also resulted in a two-fold increase of UA concentrations suggesting that the ECS-induced UA increase is related to the seizure activity per se. Local administration of tetrodotoxin or perfusion with a Ca(2+)-free solution failed to affect the basal or the ECS-induced increase in UA concentrations. These data indicate that both the basal and the stimulated interstitial concentrations of uric acid are not dependent upon neuronal activity and exocytotic release. The UA response to ECS appears to be refractory to a second ECS delivered 2 but not 24 h after the first. Intrastriatal infusion of allopurinol (1 mM), an inhibitor of UA synthesis, decreased basal UA concentrations to 26% but did not influence the ECS-induced UA increase. Systemic injection of allopurinol (20 mg/kg, i.p.) decreased basal UA concentrations to 25% and prevented the ECS-induced UA elevation. ECS also increased serum concentrations of UA to almost 200% of baseline. Allopurinol (20 mg/kg, i.p.) markedly decreased serum UA concentrations to non-detectable levels and completely abolished the ECS-induced increase. The estimated concentration difference between blood and brain interstitial UA strongly suggests that ECS-induced increase in brain interstitial UA concentrations is of peripheral origin possibly due to disruption of the blood brain barrier during seizure activity.
Nomikos
G G
GG
Department of Psychiatry, University of British Columbia, Vancouver, Canada.
Zis
A P
AP
Damsma
G
G
Fibiger
H C
HC
D000287:Administration, Topical; D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000502:physiology; D004597:Electroshock; D005110:Extracellular Space / Q000378:metabolism*; D005481:Flurothyl / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014527:Uric Acid / Q000097:blood / Q000378:metabolism*
D014527:Uric Acid; D013779:Tetrodotoxin; D000493:Allopurinol; D005481:Flurothyl