Differential effects of 3-PPP enantiomers on extracellular dopamine concentration in the caudate-putamen and nucleus accumbens of rats.

The ability of the enantiomers of 3-PPP (3-(3-hydroxyphenyl)-N-n-propylpiperidine) to modify the extracellular concentration of dopamine (DA) in the caudate-putamen and the nucleus accumbens of awake rats was assessed using intracranial microdialysis. The enantiomers and the racemate were directly infused at 3 incremental concentrations (1-100 microM) or systematically administered by subcutaneous injection (10 mg/kg). Both systemic administration and direct infusion of (-)3-PPP at the highest concentration (100 microM) significantly increased extracellular DA in both brain regions. This increase was also seen in the presence of higher extracellular DA levels following reuptake inhibition by nomifensine (10 microM). In contrast to the effects of (-)3-PPP, systemic administration of both (+)3-PPP and (+/-)3-PPP decreased DA levels. Infusion of (+/-)3-PPP led to slight increases in DA levels in both brain regions at the highest concentration (100 microM), while (+)3-PPP at 100 microM also produced a significant increase in the caudate-putamen, but not in the nucleus accumbens. However, in the presence of nomifensine-induced elevations in extracellular DA, (+)3-PPP produced a significant decrease in DA concentrations in both brain regions. These results support previous findings that the enantiomers of 3-PPP show unique profiles in their in vivo effects on DA terminal functions. Furthermore, these effects are dependent on the mode of 3-PPP administration, the brain region in which DA overflow is measured, and the level of basal extracellular DA.