TIME-COURSE OF RECOVERY OF EXTRACELLULAR DOPAMINE FOLLOWING PARTIAL DAMAGE TO THE NIGROSTRIATAL DOPAMINE SYSTEM

Partial damage to the nigrostriatal dopamine (DA) system can produce s evere behavioral deficits, from which animals gradually recover. Altho ugh the compensatory neuroadaptations that contribute to recovery of f unction have received considerable attention, the exact role of presyn aptic versus postsynaptic contributions remains unclear. For example, it has been suggested that presynaptic adaptations may not be sufficie nt to account for recovery of function, because compensatory increases in DA biosynthesis, metabolism, and release are maximal within 3 d fo llowing a unilateral 6-hydroxydopamine (6-OHDA) lesion, before behavio ral recovery is complete. The purpose of this study was to examine ano ther presynaptic adaptation, the normalization of extracellular DA. if this is also complete within 3 d postlesion, it, too, would be insuff icient to account for the protracted time course of behavioral recover y. But if the normalization of extracellular DA proceeds more graduall y, it could potentially account for the time course behavioral recover y. To address this issue, the extracellular concentration of striatal DA ipsilateral and contralateral to a unilateral 6-OHDA lesion was est imated with microdialysis, either 4 d or 3-4 weeks following the lesio n. After estimating the basal extracellular concentration of DA, the a bility to increase DA release further was assessed by administering an amphetamine challenge. It was found that in animals with a 6-OHDA les ion, the concentration of DA in dialysate was higher than would be pre dicted by the extent of DA denervation. Furthermore, in groups matched for lesion size, extracellular DA was significantly higher 3-4 weeks following a 6-OHDA lesion than 4 d following the lesion. These finding s suggest that the normalization of extracellular DA may be a relative ly gradual process, and therefore may be sufficient to account for the protracted time course of behavioral recovery.