Changes in striatal dopamine neurotransmission assessed with microdialysis following recovery from a bilateral 6-OHDA lesion: variation as a function of lesion size

摘要

Intracerebral microdialysis was used to measure the extracellular concentration of striatal dopamine (DA) and its metabolites in freely moving rats depleted of DA by the bilateral infusion of 6- hydroxydopamine into the substantia nigra approximately 1 month earlier. It was found that the basal extracellular concentration of DA remained within the same range as seen in control animals until the size of the lesion exceeded 80% (estimated by the postmortem tissue concentration of DA). In animals with an 80–95% lesion there was only a modest decrease in basal extracellular DA, but as lesion size exceeded 95% there was a marked drop in the basal extracellular concentration of DA. In contrast, the basal extracellular concentration of the DA metabolites showed a more steady decline as a function of lesion size. To determine the ability of the residual population of DA terminals to further increase DA release upon increased demand, animals were given a challenge injection of 1.5 mg/kg of d-amphetamine. Amphetamine-evoked DA release remained within the control range until lesion size exceeded 95%. These results provide direct confirmation for the hypothesis that following recovery from partial bilateral damage to the nigrostriatal DA system in adulthood, there are presynaptic compensatory changes in the remaining population of DA neurons sufficient to “normalize” the extracellular concentration of striatal DA. It is suggested that this normalization of extracellular DA is responsible for the sparing of function seen following the loss of up to 80% of the DA innervation to the striatum and contributes to the recovery of function seen after even more extensive damage (80–95%).(ABSTRACT TRUNCATED AT 250 WORDS)