Journal of Neuroscience, Vol 14, 2687-2696, Copyright © 1994 by Society for Neuroscience
Time course of recovery of extracellular dopamine following partial damage to the nigrostriatal dopamine system
TE Robinson, Z Mocsary, DM Camp and IQ Whishaw
Department of Psychology, University of Michigan, Ann Arbor 48104-1687.
Partial damage to the nigrostriatal dopamine (DA) system can produce severe
behavioral deficits, from which animals gradually recover. Although the
compensatory neuroadaptations that contribute to recovery of function have
received considerable attention, the exact role of presynaptic versus
postsynaptic contributions remains unclear. For example, it has been
suggested that presynaptic adaptations may not be sufficient to account for
recovery of function, because compensatory increases in DA biosynthesis,
metabolism, and release are maximal within 3 d following a unilateral
6-hydroxydopamine (6-OHDA) lesion, before behavioral recovery is complete.
The purpose of this study was to examine another presynaptic adaptation,
the normalization of extracellular DA. If this is also complete within 3 d
postlesion, it, too, would be insufficient to account for the protracted
time course of behavioral recovery. But if the normalization of
extracellular DA proceeds more gradually, it could potentially account for
the time course behavioral recovery. To address this issue, the
extracellular concentration of striatal DA ipsilateral and contralateral to
a unilateral 6-OHDA lesion was estimated with microdialysis, either 4 d or
3-4 weeks following the lesion. After estimating the basal extracellular
concentration of DA, the ability to increase DA release further was
assessed by administering an amphetamine challenge. It was found that in
animals with a 6-OHDA lesion, the concentration of DA in dialysate was
higher than would be predicted 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 findings suggest that the normalization of extracellular
DA may be a relatively gradual process, and therefore may be sufficient to
account for the protracted time course of behavioral recovery.
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