Alteration in L-DOPA evoked dopamine and DOPAC output under conditions of impaired vesicular dopamine storage

We examined the effect of L-dihydroxyphenylalanine (L-DOPA) infusion in vit ro upon dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) output from su perfused corpus striatum of vehicle and reserpine or tetrabenazine (TBZ) tr eated male rats. Specifically, we tested the effects of two 20-min infusion s of L-DOPA (5 uM) upon DA and DOPAC output (pg/mg/min) in reserpine (5 mg/ kg, i.p., 24 hours before sacrifice; n = 11), TBZ (30 mg/kg, i.p. 1 hour be fore sacrifice, n 8) or vehicle (n = 21) treated rats. There was an overall significantly higher L-DOPA evoked DA output from the vehicle (12.22 +/- 1 .74) versus reserpine (4.39 +/- 2.40) (p < 0.05). but not TBZ (9.16 +/- 12. 81) treated rats. In addition, the DA response to the second L-DOPA infusio n was significantly increased over that of the first response in the vehicl e (9.40 +/- 2.11 vs. 15.04 +/- 2.78) (p < 0.05), but not reserpine or TBZ t reated rats. The overall DOPAC outputs did not achieve a statistically sign ificant difference among all treatment groups. However, the DOPAC outputs f ollowing the second L-DOPA infusion were significantly reduced in reserpine (41.15 +/- 6.10 vs. 20.27 +/- 4.54) and TBZ (21.38 +/- 4.41 vs. 10.57 +/- 2.36) (both p < 0.05), but not vehicle (28.99 +/- 4.00 vs. 24.91 +/- 4.78) treated rats. We conclude that: 1) the storage capacity of DA neurons is on e of the important elements involved in affecting L-DOPA's effects upon DA and DOPAC output, 2) the shunting of storage to metabolism may represent a common characteristic in impaired nigrostriatal dopaminergic system, and 3) TBZ may operate differently fi-om reserpine in the nigrostriatal dopaminer gic system.