ESTIMATING EXTRACELLULAR CONCENTRATIONS OF DOPAMINE AND 3,4-DIHYDROXYPHENYLACETIC ACID IN NUCLEUS-ACCUMBENS AND STRIATUM USING MICRODIALYSIS - RELATIONSHIPS BETWEEN IN-VITRO AND IN-VIVO RECOVERIES

It is common practice in microdialysis studies for probes to be ''cali brated'' in artificial CSF and in vitro recoveries determined for all substances to be measured in vivo. Dialysate concentrations of such su bstances are then ''corrected'' for in vitro recoveries to provide ''e stimates'' of extracellular concentrations. At least for dopamine, in vitro and in vivo recoveries are significantly different and, therefor e, an estimate of extracellular dopamine based on correction for in vi tro recovery is likely to be erroneous. Generally, however, the relati ve relationships of such estimates among animals are of interest rathe r than the ''true'' extracellular values. Such relationships would be valid to the extent that estimated values are correlated with or predi ctive of true values. Using the ''no net flux'' procedure, the present study sought to determine, for both dopamine and its metabolite 3,4-d ihydroxyphenylacetic acid (DOPAC), whether in vitro and in vivo recove ries would correlate with each other as well as whether respective est imated and true (no net flux) values of these substances would correla te with each other. Probes (3 mm; BAS/CMed MF-5393), previously calibr ated, were lowered into both the nucleus accumbens and striatum of fre ely moving rats the day before sample collection was begun. In vitro a nd in vivo recoveries were not significantly correlated (r = 0.1-0.3), for either dopamine or DOPAC. For both dopamine and DOPAC, however, t here were significant correlations (r = 0.7-0.8) between estimated and true values. Surprisingly, when using these commercial probes, absolu te dialysate levels for both substances were even better correlated (r = 0.9-0.95) with true values. This suggests that, with these probes, a direct comparison of dialysate concentrations can be used to determi ne relative changes in basal extracellular levels of dopamine and DOPA C when it is not practical to do no net flux studies (e.g., because of the time required to characterize a drug effect). The use of in vitro calibrations adjusts the values closer to the true values but also ad ds noise to each value and therefore should be avoided.