Abstract
Purpose: The present study assessed the influence of L-DOPA administration on neostriatal dopamine (DA) transporter (DAT) binding in relation to motor and exploratory behaviors in the rat.Methods: Rats received injections of 5 mg/kg L-DOPA, 10 mg/kg L-DOPA or vehicle. Motor and exploratory behaviors were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. Dopamine transporter binding was measured with small animal single-photon emission computed tomography (SPECT) 2 h after radioligand administration for 60 min.Results: Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle. Moreover, 10 mg/kg L-DOPA induced less distance traveled and ambulation than 5 mg/kg L-DOPA. Analysis of time-behavior (t-b) curves showed that L-DOPA-treated animals relative to vehicle exhibited (1) a faster rate of increase in duration of sitting; (2) a slower rate of increase in duration of head-shoulder motility; and (3) a slower rate of decrease in frequency of head-shoulder motility.Conclusions: The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA. L-DOPA-treated animals showed less head-shoulder motility and more sitting than vehicle-treated animals, indicating an association between less behavioral activity and increased availability of striatal DA. The faster increase of sitting duration to a higher final level and the slower increase of head-shoulder motility to a lower final level relative to controls may be interpreted in terms on behavioral habituation to a novel environment.
Highlights
Presynaptic monoamine transporters such as the dopamine transporter (DAT) regulate neurotransmitter concentrations available for receptor binding at the postsynaptic site
Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle
The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA
Summary
Presynaptic monoamine transporters such as the dopamine transporter (DAT) regulate neurotransmitter concentrations available for receptor binding at the postsynaptic site. Deficiencies of DAT function play a major role in the pathophysiology of psychiatric disorders (for review see, e.g., Nikolaus et al, 2009b, 2010, 2012, 2014) and a variety of neurological conditions (for review see, e.g., Nikolaus et al, 2009a) including idiopathic and early-onset Parkinson’s disease (PD) and the “Parkinson Plus” syndromes multiple system atrophy and progressive supranuclear palsy. The treatment of choice for idiopathic PD is L-3,4dihydroxyphenylalanine (L-DOPA), which passes the blood-brain barrier via a saturable transporter and is converted to dopamine (DA) in the presynaptic terminal by aromatic L-amino acid decarboxylase (for review see Okereke, 2002). Common features of long-term treatment with L-DOPA, are dyskinesias, on-off phenomenon and wearing-off phenomenon (for review see Cenci et al, 2011)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
