Presynaptic dopaminergic compartment determines the susceptibility to L-DOPA-induced dyskinesia in rats.

ABSTRACT: Drug-induced dyskinesias in dopamine-denervated animals are known to depend on both pre- and postsynaptic changes of the nigrostriatal circuitry. In lesion models used thus far, changes occur in both of these compartments and, therefore, it has not been possible to dissect the individual contribution of each compartment in the pathophysiology of dyskinesias. Here we silenced the nigrostriatal dopamine neurotransmission without affecting the anatomical integrity of the presynaptic terminals using a short-hairpin RNA-mediated knockdown of tyrosine hydroxylase enzyme (shTH). This treatment resulted in significant reduction (by about 70%) in extracellular dopamine concentration in the striatum as measured by on-line microdialysis. Under these conditions, the animals remained nondyskinetic afte

SUBMITTER: Ulusoy A 

PROVIDER: S-EPMC2919904 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature