Difference in extracellular cocaine concentration between the ventral tegmental area and the medial prefrontal cortex following intravenous administration as revealed by quantitative microdialysis coupled with in vivo calibration.
Two microdialysis probes (active length: 1 mm) were simultaneously lowered into the ventral tegmental area (VTA) and the medial prefrontal cortex (mPFC) of each male, adult Sprague-Dawley rat, anesthetized with chloral hydrate, to evaluate whether cocaine distribution between these two areas is uniform after i.v. injection of 3 mg/kg cocaine. Using a modified in vivo calibration method, we can estimate the extracellular cocaine concentration in those nuclei. This proposed calibration method offers the advantages of simplicity and speed. Measurement of the cocaine concentration in the dialysate and estimation of the extracellular cocaine concentration showed that extracellular cocaine in the VTA was significantly higher than that in the mPFC. Next, the active length of the dialysis probe was extended to 4 mm in order to examine the effect of the active probe length on the cocaine distribution profile between the mPFC and a mixed area of VTA and red nucleus. Surprisingly, the cocaine concentration in dialysate had a contradictory result compared to the extracellular cocaine concentration due to in vivo recovery in the mPFC (25.3 +/- 3.1%) which was significantly higher than that in the mixed area (17.5 +/- 1.6%). Firstly, these results suggest that distribution of cocaine following systemic administration was not uniform in the rat brain. Secondly, in a valid comparison of drug concentrations between the two dialysis areas, we must consider the in vivo recovery for each brain region.
Pan
W H
WH
Institute of Pharmacology, National Yang-Ming Medical College, Taipei, Taiwan, ROC.
Lim
L H
LH
Shiau
M R
MR
D000818:Animals; D002138:Calibration; D003042:Cocaine / Q000032:analysis / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000737:chemistry*; D005625:Frontal Lobe / Q000737:chemistry*; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013681:Tegmentum Mesencephali / Q000737:chemistry*
D003042:Cocaine