The effect of inhibition of synthesis, release, metabolism and uptake on the microdialysis extraction fraction of dopamine.

The present study was designed to determine the effects that synthesis, release, metabolism and uptake have on the in vivo extraction fraction (relative recovery) of dopamine (DA) in the nucleus accumbens of the rat. The extraction fraction and extracellular concentration of DA were established for rats that were perfused with artificial cerebrospinal fluid (aCSF) with or without substances inhibiting synthesis (100 microM alpha-methylparatyrosine (alpha-MPT)), release (1 microM tetrodotoxin (TTX)), uptake (1 microM, 20 microM cocaine or 1 microM GBR-12909) or metabolism (100 microM tropolone or 100 microM pargyline) with DA concentrations ranging from 0 to 200 nM. Inhibiting synthesis with alpha-MPT or release with TTX had no effect on the extraction fraction of DA. Inhibiting intracellular or extracellular metabolism with pargyline or tropolone, respectively, did not cause any changes in the extraction fraction. However, inhibiting uptake with 20 microM cocaine or 1 microM GBR-12909 decreased the extraction fraction by one-third and one-half, respectively. These results provide evidence that uptake is the primary neuronal process affecting the extraction fraction of DA in the nucleus accumbens and indicate that the extraction fraction may be useful as an index of DA uptake in vivo.