Evaluation of metaquant microdialysis for measurement of absolute concentrations of amphetamine and dopamine in brain: a viable method for assessing pharmacokinetic profile of drugs in the brain.
Direct measurement of absolute brain concentration of amphetamine and dopamine were obtained using metaquant (MQ) microdialysis, which achieves near 100% recovery, in the caudate nucleus. Conventional microdialysis monoprobes were also implanted in the caudate nucleus in the contralateral side of the same animals to compare the brain concentrations obtained from these two probe types. In addition plasma concentrations of amphetamine were obtained simultaneously from the same animals. The distribution of amphetamine in the plasma and of amphetamine and dopamine in both probe types followed same profile at each time interval. The basal dialysate concentration of dopamine in the caudate nucleus measured by MQ, was 9.40+/-0.60 nM, while measured by conventional microdialysis it was 6.35+/-0.36 nM. This study demonstrates that MQ microdialysis is an appropriate method for determination of true extracellular levels of drugs and neurotransmitters in the brain, under dynamic conditions. Since these measurements, together with measurements of plasma concentrations of the drug, can be made in a single animal, the method can be used to study pharmacokinetic-pharmacodyamics profile of psychoactive agents.
Sood
Pooja
P
School of Psychology, University of Leicester, Leicester, UK. ps151@le.ac.uk
Cole
Susan
S
Fraier
Daniela
D
Young
Andrew M J
AM
D000661:Amphetamine / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods; D001923:Brain Chemistry / Q000502:physiology*; D002421:Caudate Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods*; D009448:Neurochemistry / Q000379:methods*; D009480:Neuropharmacology / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000661:Amphetamine; D004298:Dopamine