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Article Title

In vivo microdialysis: A novel sampling technique for drug analysis in live subjects

Abstract

By using an in vivo microdialysis technique, extracellular dopamine (DA) and cocaine concentration in the medial prefrontal cortex (mPFC) after intravenous cocaine injection (1.5 mg/kg in group A and 3.0 mg/kg in group B) were evaluated in adult male Sprague-Dawley rats anesthetized with chloral hydrate (400 mg/kg, i.p., with 80 mg/kg/h supplements). Dialysate samples were collected at 20-min intervals for a 100-min period and were analyzed for DNA content by an HPLC/electrochemical detector, and for cocaine content by an HPLC/ultraviolet detector. After intravenous (i.v.) cocaine injection, both DA and cocaine concentrations in the dialysate reached maximum within 20 minutes, correlated nicely, and then rapidly declined. The maximal DA increase was 214.0 ± 20.3% for the high dose group and 118.7 ± 5.0% for the low dose group. The DA baseline concentration in dialysate was 0.390 ± 0.058 nM. The maximal cocaine concentration was 0.20 ± 0.08 μM, and 0.6 ± 0.08 μM respectively. By using an in vivo calibration method for microdialysis, the in vivo recovery of cocaine in the mPFC was obtained as 33 ± 5%. The actual extracellular cocaine concentration was therefore calculated to be 1.84 ± 0.64 μM in group A and 4.00 ± 0.94 μgM in group B. From the results, extracellular cocaine concentration was found to be highly correlated with a DA percentile increase over the 100 min period of time. After first-order linear regression, the correlation coefficient was 0.976. In summary, in vivo microdialysis is not only a sampling technique for determining the drug concentration at a specific area in live subjects, but is also useful simultaneously to observe the changes of endogenous compound. Therefore, microdialysis technique is a popular research tool with great potential in the immediate future and is a valuable new state of the art to be introduced into our research society.

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