Compensatory increase in extracellular dopamine in the nucleus accumbens of adult rats with neonatal 6-hydroxydopamine treatment.

To characterize a compensatory function of the dopaminergic system of residual dopamine (DA) neurons in the mesolimbic pathway with DA-depleting lesions, we compared tissue and extracellular concentrations of DA and its metabolites in the nucleus accumbens (NACC) of adult rats with neonatal 6-hydroxydopamine (6-OHDA) treatment with those of control rats with neonatal vehicle treatment using high-performance liquid chromatography. The tissue concentration of DA for 6-OHDA-treated rats was 26.9% of that for the control rats, whereas the extracellular DA was not significantly different from the controls. Furthermore, the extracellular DA concentration in the NACC of 6-OHDA-treated rats was significantly increased compared to the controls following neurotensin (NT) microinjection into the ventral tegmental area (VTA). These results suggest that the extracellular DA of the adult rat brain following neonatal 6-OHDA treatment was compensated for by increasing the release of DA from terminals in the NACC of remaining DA neurons through increased mesolimbic pathway afferents (increased demand), as well as by decreasing the synaptic DA reuptake sites and/or D4 receptors. This study supports our hypothesis that the compensatory mechanism(s) of remaining DA neurons in the mesolimbic system are underlying in behavioral characteristics of adult rats with neonatal depletion of brain DA.