A novel system allowing long-term simultaneous video-electroencephalography recording, drug infusion and blood sampling in rats.
BACKGROUND
Electroencephalography (EEG) recording and drug administration is commonly used for neurological experiments in rats, but is typically cumbersome due the use of multiple lines. We have developed a unique system, which allows long-term simultaneous video-electroencephalography recording, drug infusion and blood sampling in rats.


METHODS
The vEEG/drug infusion system was designed and tested on two contrasting animal models of epilepsy. Animals were implanted with EEG-electrodes and a jugular vein cannula fixed in a head cap, avoiding an additional cable for tethering. In an acute infusion study (n=16), repeated blood samples were taken after i.v. bolus injection of valproate. In a subset of these rats (n=10), paired blood samples were removed from the jugular vein and the heart after valproate administration. In a chronic infusion study (n=38), heparinised (4IU/h) saline or valproate (42mg/kg/h) was infused continuously for up to 17 days.


RESULTS
In the acute study, repeated blood samples showed a decrease in plasma valproate levels over time following bolus injection. In the chronic study, high quality continuous EEG was achieved and 79% of animals were successfully infused throughout the planned infusion period (13-17 days), with 66% of projected blood samples able to be taken during the infusion. There was a high correlation between the jugular vein and cardiac plasma levels of valproate (Spearman test, r=0.69; p<0.05).


CONCLUSIONS
This system is ideal for pharmacokinetic/dynamic studies and long-term drug infusion where simultaneous EEG and/or frequent blood sampling are desired.
The Department of Medicine, The University of Melbourne, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Leena
L
van Raay
Margaret Joan
MJ
Morris
Ronald Charles
RC
Reed
Terence John
TJ
O'Brien
Stefanie
S
Dedeurwaerdere
D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics; D001800:Blood Specimen Collection / Q000379:methods*; D002404:Catheterization; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004569:Electroencephalography / Q000379:methods*; D004827:Epilepsy / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D007262:Infusions, Intravenous / Q000379:methods; D007601:Jugular Veins / Q000033:anatomy & histology / Q000502:physiology / Q000601:surgery; D008297:Male; D009480:Neuropharmacology / Q000295:instrumentation* / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000097:blood / Q000493:pharmacokinetics; D014741:Video Recording / Q000379:methods*
D000927:Anticonvulsants; D014635:Valproic Acid