The in vivo microdialysis recovery of dopamine is altered independently of basal level by 6-hydroxydopamine lesions to the nucleus accumbens

Abstract

The present study was designed to test the hypothesis that the active neurotransmitter processes of release and uptake affect the in vivo microdialysis recovery of dopamine (DA) in the nucleus accumbens (N ACC) of the rat. The in vivo recovery for DA was established for rats which had received either unilateral infusions of the neurotoxin 6-hydroxydopamine (6-OHDA, 8 μg) or vehicle (0.2 μg ascorbate). In the quantitative dialysis method used (point of no net flux method), DA is added to the perfusate at concentrations above and below the expected extracellular concentration (0, 5, 10 and 20 nM) and DA is measured in the dialysate from the brain to generate a series of points. A linear fit is performed, the slope of which is the in vivo recovery of the dialysis probe. The in vivo recovery of the 6-OHDA group was 30 ± 3% which was significantly lower ( P < 0.002) than the in vivo recovery of the control group which was 60 ± 3% (mean ± SEM; n = 6/group). The zero intercept of this regression is the point of no net flux, which is the extracellular concentration of DA independent of the probe sampling characteristics. The extracellular DA concentration for the 6-OHDA group was 7.8 ± 1.1nM, which was not significantly different than the control group which was 6.9 ± 0.7nM. The tissue DOPAC/DA ratios of the 6-OHDA lesioned hemispheres were significantly higher than the contralateral hemispheres of the same animals (0.62 ± 0.1vs.0.27 ± 0.1; P < 0.02) while the DOPAC/DA ratios in the control group were not significantly different (0.24 ± 0.1vs.0.27 ± 0.1). The fractional DA efflux from the terminals in the 6-OHDA group was significantly higher than the fractional DA efflux of the control group (0.52 ± 0.08vs.0.03 ± 0.003; P < 0.0001), indicating that the remaining terminals have increased turnover of DA. Despite the increased turnover, however, the number of remaining release and uptake sites are not sufficient to maintain the high in vivo recovery observed in the control group.